@article {pmid37239339, year = {2023}, author = {Wu, Z and Yang, T and Qin, R and Liu, H}, title = {Complete Mitogenome and Phylogenetic Analysis of the Carthamus tinctorius L.}, journal = {Genes}, volume = {14}, number = {5}, pages = {}, doi = {10.3390/genes14050979}, pmid = {37239339}, issn = {2073-4425}, abstract = {Carthamus tinctorius L. 1753 (Asteraceae), also called safflower, is a cash crop with both edible and medical properties. We analyzed and reported the safflower mitogenome based on combined short and long reads obtained from Illumina and Pacbio platforms, respectively. This safflower mitogenome mainly contained two circular chromosomes, with a total length of 321,872 bp, and encoded 55 unique genes, including 34 protein-coding genes (PCGs), 3 rRNA genes, and 18 tRNA genes. The total length of repeat sequences greater than 30 bp was 24,953 bp, accounting for 7.75% of the whole mitogenome. Furthermore, we characterized the RNA editing sites of protein-coding genes located in the safflower mitogenome, and the total number of RNA editing sites was 504. Then, we revealed partial sequence transfer events between plastid and mitochondria, in which one plastid-derived gene (psaB) remained intact in the mitogenome. Despite extensive arrangement events among the three mitogenomes of C. tinctorius, Arctium lappa, and Saussurea costus, the constructed phylogenetic tree based on mitogenome PCGs showed that C. tinctorius has a closer relationship with three Cardueae species, A. lappa, A. tomentosum, and S. costus, which is similar to the phylogeny constructed from the PCGs of plastid genomes. This mitogenome not only enriches the genetic information of safflower but also will be useful in the phylogeny and evolution study of the Asteraceae.}, } @article {pmid37231782, year = {2023}, author = {Shi, J and Yan, S and Li, W and Yang, X and Cui, Z and Li, J and Li, G and Li, Y and Hu, Y and Gao, S}, title = {PacBio full-length transcriptome analysis provides new insights into transcription of chloroplast genomes.}, journal = {RNA biology}, volume = {20}, number = {1}, pages = {248-256}, doi = {10.1080/15476286.2023.2214435}, pmid = {37231782}, issn = {1555-8584}, abstract = {Chloroplast and mitochondrial DNA (cpDNA and mtDNA) are apart from nuclear DNA (nuDNA) in a eukaryotic cell. The transcription system of chloroplasts differs from those of mitochondria and eukaryotes. In contrast to nuDNA and animal mtDNA, the transcription of cpDNA is still not well understood, primarily due to the unresolved identification of transcription initiation sites (TISs) and transcription termination sites (TTSs) on the genome scale. In the present study, we characterized the transcription of chloroplast (cp) genes with greater accuracy and comprehensive information using PacBio full-length transcriptome data from Arabidopsis thaliana. The major findings included the discovery of four types of artifacts, the validation and correction of cp gene annotations, the exact identification of TISs that start with G, and the discovery of polyA-like sites as TTSs. Notably, we proposed a new model to explain cp transcription initiation and termination at the whole-genome level. Four types of artifacts, degraded RNAs and splicing intermediates deserve the attention from researchers working with PacBio full-length transcriptome data, as these contaminant sequences can lead to incorrect downstream analysis. Cp transcription initiates at multiple promoters and terminates at polyA-like sites. Our study provides new insights into cp transcription and new clues to study the evolution of promoters, TISs, TTSs and polyA tails of eukaryotic genes.}, } @article {pmid37221926, year = {2023}, author = {Dong, X and Zhang, H and Zhu, X and Wang, K and Xue, H and Ye, Z and Zheng, C and Bu, W}, title = {Mitochondrial introgression and mito-nuclear discordance obscured the closely related species boundaries in Cletus Stål from China (Heteroptera: Coreidae).}, journal = {Molecular phylogenetics and evolution}, volume = {184}, number = {}, pages = {107802}, doi = {10.1016/j.ympev.2023.107802}, pmid = {37221926}, issn = {1095-9513}, mesh = {Animals ; *Heteroptera ; Phylogeny ; China ; *Genome, Mitochondrial ; Mitochondria ; Mitomycin ; }, abstract = {Accurate taxonomy and delimitation are of great importance for pest control strategies and management programs. Here, we focus on Cletus (Insecta: Hemiptera: Coreidae), which includes many crop pests. The species boundaries still conflict and only cytochrome c oxidase subunit I (COI) barcoding has been previously used for molecular studies. We generated new mitochondrial genome and nuclear genome-wide SNPs to explore the species boundaries of 46 Cletus samples from China using multiple species delimitation approaches. All results recovered a monophyly with high support, except for two closely related species in clade I - C. punctiger and C. graminis. Mitochondrial data demonstrated admixture in clade I, while genome-wide SNPs unambiguously identified two separate species, which were confirmed by morphological classification. Inconsistent nuclear and mitochondrial data indicated mito-nuclear discordance. Mitochondrial introgression is the most likely explanation, and more extensive sampling and more comprehensive data are needed to ascertain a pattern. Accurate species delimitation will shed light on species status; thus, an accurate taxonomy is of particular concern, as there is a pressing need to implement precise control of agricultural pests and to perform further research on diversification.}, } @article {pmid36638953, year = {2023}, author = {Gnocchi, D and Sabbà, C and Mazzocca, A}, title = {Lactic acid fermentation: A maladaptive mechanism and an evolutionary throwback boosting cancer drug resistance.}, journal = {Biochimie}, volume = {208}, number = {}, pages = {180-185}, doi = {10.1016/j.biochi.2023.01.005}, pmid = {36638953}, issn = {1638-6183}, mesh = {Humans ; *Lactic Acid/metabolism ; Fermentation ; Glycolysis ; Mitochondria/metabolism ; *Neoplasms/drug therapy/genetics/metabolism ; Drug Resistance, Neoplasm/genetics ; }, abstract = {After four decades of research primarily focused on tumour genetics, the importance of metabolism in tumour biology is receiving renewed attention. Cancer cells undergo energy, biosynthetic and metabolic rewiring, which involves several pathways with a prevalent change from oxidative phosphorylation (OXPHOS) to lactic acid fermentation, known as the Warburg effect. During carcinogenesis, microenvironmental changes can trigger the transition from OXPHOS to lactic acid fermentation, an ancient form of energy supply, mimicking the behaviour of certain anaerobic unicellular organisms according to "atavistic" models of cancer. However, the role of this transition as a mechanism of cancer drug resistance is unclear. Here, we hypothesise that the metabolic rewiring of cancer cells to fermentation can be triggered, enhanced, and sustained by exposure to chronic or high-dose chemotherapy, thereby conferring resistance to drug therapy. We try to expand on the idea that metabolic reprogramming from OXPHOS to lactate fermentation in drug-resistant tumour cells occurs as a general phenotypic mechanism in any type of cancer, regardless of tumour cell heterogeneity, biodiversity, and genetic characteristics. This metabolic response may therefore represent a common feature in cancer biology that could be exploited for therapeutic purposes to overcome chemotherapy resistance, which is currently a major challenge in cancer treatment.}, } @article {pmid37221210, year = {2023}, author = {Paukszto, Ł and Górski, P and Krawczyk, K and Maździarz, M and Szczecińska, M and Ślipiko, M and Sawicki, J}, title = {The organellar genomes of Pellidae (Marchantiophyta): the evidence of cryptic speciation, conflicting phylogenies and extraordinary reduction of mitogenomes in simple thalloid liverwort lineage.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {8303}, pmid = {37221210}, issn = {2045-2322}, mesh = {*Hepatophyta ; *Genome, Mitochondrial ; Phylogeny ; Mitochondria ; *Genome, Plastid ; *Anemone ; }, abstract = {Organellar genomes of liverworts are considered as one of the most stable among plants, with rare events of gene loss and structural rearrangements. However, not all lineages of liverworts are equally explored in the field of organellar genomics, and subclass Pellidae is one of the less known. Hybrid assembly, using both short- and long-read technologies enabled the assembly of repeat-rich mitogenomes of Pellia and Apopellia revealing extraordinary reduction of length in the latter which impacts only intergenic spacers. The mitogenomes of Apopellia were revealed to be the smallest among all known liverworts-109 k bp, despite retaining all introns. The study also showed the loss of one tRNA gene in Apopellia mitogenome, although it had no impact on the codon usage pattern of mitochondrial protein coding genes. Moreover, it was revealed that Apopellia and Pellia differ in codon usage by plastome CDSs, despite identical tRNA gene content. Molecular identification of species is especially important where traditional taxonomic methods fail, especially within Pellidae where cryptic speciation is well recognized. The simple morphology of these species and a tendency towards environmental plasticity make them complicated in identification. Application of super-barcodes, based on complete mitochondrial or plastid genomes sequences enable identification of all cryptic lineages within Apopellia and Pellia genera, however in some particular cases, mitogenomes were more efficient in species delimitation than plastomes.}, } @article {pmid37199915, year = {2023}, author = {Begeman, A and Babaian, A and Lewis, SC}, title = {Metatranscriptomic analysis uncovers prevalent viral ORFs compatible with mitochondrial translation.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0100222}, doi = {10.1128/msystems.01002-22}, pmid = {37199915}, issn = {2379-5077}, abstract = {RNA viruses are ubiquitous components of the global virosphere, yet relatively little is known about their genetic diversity or the cellular mechanisms by which they exploit the biology of their diverse eukaryotic hosts. A hallmark of (+)ssRNA viruses is the ability to remodel host endomembranes for their own replication. However, the subcellular interplay between RNA viruses and host organelles that harbor gene expression systems, such as mitochondria, is complex and poorly understood. Here we report the discovery of 763 new virus sequences belonging to the family Mitoviridae by metatranscriptomic analysis, the identification of previously uncharacterized mitovirus clades, and a putative new viral class. With this expanded understanding of the diversity of mitovirus and encoded RNA-dependent RNA polymerases, we annotate mitovirus-specific protein motifs and identify hallmarks of mitochondrial translation, including mitochondrion-specific codons. This study expands the known diversity of mitochondrial viruses, and provides additional evidence that they co-opt mitochondrial biology for their survival.IMPORTANCEMetatranscriptomic studies have rapidly expanded the cadre of known RNA viruses, yet our understanding of how these viruses navigate the cytoplasmic milieu of their hosts to survive remains poorly characterized. In this study, we identify and assemble 763 new viral sequences belonging to the Mitoviridae, a family of (+)ssRNA viruses thought to interact with and remodel host host mitochondria. We exploit this genetic diversity to identify new clades of Mitoviridae, annotate clade-specific sequence motifs that distinguish the mitoviral RNA-dependent RNA polymerase, and reveal patterns of RdRp codon usage consistent with translation on host cell mitoribosomes. These results serve as a foundation for understanding how mitoviruses co-opt mitochondrial biology for their proliferation.}, } @article {pmid37127113, year = {2023}, author = {Hausdorf, B and Xu, J}, title = {Speciation of rock-dwelling snail species: Disjunct ranges and mosaic patterns reveal the importance of long-distance dispersal in Chilostoma (Cingulifera) in the European Southern Alps.}, journal = {Molecular phylogenetics and evolution}, volume = {184}, number = {}, pages = {107788}, doi = {10.1016/j.ympev.2023.107788}, pmid = {37127113}, issn = {1095-9513}, mesh = {Animals ; Phylogeny ; *Snails/genetics ; Europe ; *Mitochondria ; Genetic Variation ; }, abstract = {To better understand the origin of the high diversity and endemism in the Southern Alps of Europe, we investigated the phylogeny and population structure of the rock-dwelling snail group Chilostoma (Cingulifera) in the Southern Alps. We generated genomic ddRAD data and mitochondrial sequences of 104 Cingulifera specimens from 28 populations and 14 other Ariantinae. Until recently, about 30 Cingulifera taxa were classified as subspecies of a single polytypic species. The phylogenetic and population genetic analyses of the ddRAD data and mitochondrial sequences revealed that Cingulifera in the Southern Alps is differentiated into three species. Each of the three Chilostoma (Cingulifera) species occupies disjunct sub-areas, which are separated by areas occupied by other Chilostoma taxa. Neighbouring populations of different species show little or no admixture. Tests indicating that the genetic differentiation of the three Cingulifera taxa cannot be explained by isolation by distance confirmed their species status. The disjunct range patterns demonstrate the importance of stochastic events such as passive long-distance dispersal for the evolution of population structure and speciation in these snails, and of priority effects and ecological competition as important factors influencing species distributions.}, } @article {pmid37044183, year = {2023}, author = {Chen, H and Huang, L and Yu, J and Miao, Y and Liu, C}, title = {Mitochondrial genome of Artemisia argyi L. suggested conserved mitochondrial protein-coding genes among genera Artemisia, Tanacetum and Chrysanthemum.}, journal = {Gene}, volume = {871}, number = {}, pages = {147427}, doi = {10.1016/j.gene.2023.147427}, pmid = {37044183}, issn = {1879-0038}, mesh = {Humans ; *Genome, Mitochondrial ; *Artemisia/genetics ; *Tanacetum/genetics ; *Chrysanthemum/genetics ; Phylogeny ; Mitochondria/genetics ; Mitochondrial Proteins/genetics ; }, abstract = {BACKGROUND: Artemisia argyi L., also known as mugwort, is a perennial herb whose leaves are commonly used as a source of traditional medicines. However, the evolution and structure of the mitochondrial genome (mitogenome) in A. argyi remain unclear. In this study, the mitogenome of A. argyi was assembled and characterized for the first time.

RESULTS: The mitogenome of A. argyi was a circular molecule of 229,354 bp. It encodes 56 genes, including 33 protein-coding genes (PCGs), 20 tRNA genes, and three rRNA genes, and three pseudogenes. Five trans-spliced introns were observed in three PCGs namely, nad1, nad2 and nad5. Repeat analysis identified 65 SSRs, 14 tandem repeats, and 167 dispersed repeats. The A. argyi mitogenome contains 12 plastid transfer sequences from 79 bp to 2552 bp. Five conserved MTPTs were identified in all 18 Asteraceae species. Comparison of mitogenome between A. argyi and one Artemisia specie and two Chrysanthemum species showed 14 conserved gene clusters. Phylogenetic analysis with organelle genomes of A. argyi and 18 other Anthemideae plants showed inconsistent phylogenetic trees, which implied that the evolutionary rates of PCGs and rrna genes derived from mitochondrion and plastid were incongruent. The Ka/Ks ratio of the 27 shared protein-coding genes in the 18 Anthemideae species are all less than 1 indicating that these genes were under the effect of purifying selection. Lastly, a total of 568 RNA editing sites in PCGs were further identified. The average editing frequency of non-synonymous changes was significantly higher than that of synonymous changes (one-sample Student's t-test, p-values ≤ 0.05) in three tissues (root, leaf and stem).

CONCLUSIONS: In this study, the gene content, genome size, genome comparison, mitochondrial plastid sequences, dN/dS analysis of mitochondrial protein-coding genes, and RNA-editing events in A. argyi mitogenome were determined, providing insights into the phylogenetic relationships of Asteraceae plant.}, } @article {pmid36841519, year = {2023}, author = {Tomita, K and Indo, HP and Sato, T and Tangpong, J and Majima, HJ}, title = {Development of a sensitive double TaqMan Probe-based qPCR Angle-Degree method to detect mutation frequencies.}, journal = {Mitochondrion}, volume = {70}, number = {}, pages = {1-7}, doi = {10.1016/j.mito.2023.02.010}, pmid = {36841519}, issn = {1872-8278}, mesh = {Humans ; Mutation Rate ; *MELAS Syndrome/genetics ; Mutation ; DNA, Mitochondrial/genetics ; *Stroke ; }, abstract = {We designed a method to examine the mutation frequencies of the A3243G mutation of mitochondrial DNA (mtDNA) in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. We performed a qPCR assay using the FAM and VIC TaqMan probes, which detect the 3243G (mutated) and 3243A (wild-type) sequences of mtDNA, respectively. The results obtained by "degree" in a series of differential mutation frequencies were used to plot a standard curve of the mutation frequency. The standard curve was then applied for qPCR assays of the desired samples. The standard deviation (%) of the samples calculated using the standard curve for the TaqMan probe was 2.4 ± 1.5%. This method could be used to examine mutation frequencies in the context of diabetes, aging, cancer, and neurodegenerative diseases.}, } @article {pmid37198654, year = {2023}, author = {Kienzle, L and Bettinazzi, S and Choquette, T and Brunet, M and Khorami, HH and Jacques, JF and Moreau, M and Roucou, X and Landry, CR and Angers, A and Breton, S}, title = {A small protein coded within the mitochondrial canonical gene nd4 regulates mitochondrial bioenergetics.}, journal = {BMC biology}, volume = {21}, number = {1}, pages = {111}, pmid = {37198654}, issn = {1741-7007}, abstract = {BACKGROUND: Mitochondria have a central role in cellular functions, aging, and in certain diseases. They possess their own genome, a vestige of their bacterial ancestor. Over the course of evolution, most of the genes of the ancestor have been lost or transferred to the nucleus. In humans, the mtDNA is a very small circular molecule with a functional repertoire limited to only 37 genes. Its extremely compact nature with genes arranged one after the other and separated by short non-coding regions suggests that there is little room for evolutionary novelties. This is radically different from bacterial genomes, which are also circular but much larger, and in which we can find genes inside other genes. These sequences, different from the reference coding sequences, are called alternatives open reading frames or altORFs, and they are involved in key biological functions. However, whether altORFs exist in mitochondrial protein-coding genes or elsewhere in the human mitogenome has not been fully addressed.

RESULTS: We found a downstream alternative ATG initiation codon in the + 3 reading frame of the human mitochondrial nd4 gene. This newly characterized altORF encodes a 99-amino-acid-long polypeptide, MTALTND4, which is conserved in primates. Our custom antibody, but not the pre-immune serum, was able to immunoprecipitate MTALTND4 from HeLa cell lysates, confirming the existence of an endogenous MTALTND4 peptide. The protein is localized in mitochondria and cytoplasm and is also found in the plasma, and it impacts cell and mitochondrial physiology.

CONCLUSIONS: Many human mitochondrial translated ORFs might have so far gone unnoticed. By ignoring mtaltORFs, we have underestimated the coding potential of the mitogenome. Alternative mitochondrial peptides such as MTALTND4 may offer a new framework for the investigation of mitochondrial functions and diseases.}, } @article {pmid37179826, year = {2023}, author = {Casanova, A and Wevers, A and Navarro-Ledesma, S and Pruimboom, L}, title = {Mitochondria: It is all about energy.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1114231}, pmid = {37179826}, issn = {1664-042X}, abstract = {Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment. The literature suggests crosstalk mechanisms between mitochondria and circadian clocks, the gut microbiota, and the immune system. They might even be the hub supporting and integrating activity across all these domains. Hence, they might be the (missing) link in both health and disease. Mitochondrial dysfunction is related to metabolic syndrome, neuronal diseases, cancer, cardiovascular and infectious diseases, and inflammatory disorders. In this regard, diseases such as cancer, Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), and chronic pain are discussed. This review focuses on understanding the mitochondrial mechanisms of action that allow for the maintenance of mitochondrial health and the pathways toward dysregulated mechanisms. Although mitochondria have allowed us to adapt to changes over the course of evolution, in turn, evolution has shaped mitochondria. Each evolution-based intervention influences mitochondria in its own way. The use of physiological stress triggers tolerance to the stressor, achieving adaptability and resistance. This review describes strategies that could recover mitochondrial functioning in multiple diseases, providing a comprehensive, root-cause-focused, integrative approach to recovering health and treating people suffering from chronic diseases.}, } @article {pmid37175542, year = {2023}, author = {Ke, SJ and Liu, DK and Tu, XD and He, X and Zhang, MM and Zhu, MJ and Zhang, DY and Zhang, CL and Lan, SR and Liu, ZJ}, title = {Apostasia Mitochondrial Genome Analysis and Monocot Mitochondria Phylogenomics.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175542}, issn = {1422-0067}, abstract = {Apostasia shenzhenica belongs to the subfamily Apostasioideae and is a primitive group located at the base of the Orchidaceae phylogenetic tree. However, the A. shenzhenica mitochondrial genome (mitogenome) is still unexplored, and the phylogenetic relationships between monocots mitogenomes remain unexplored. In this study, we discussed the genetic diversity of A. shenzhenica and the phylogenetic relationships within its monocotyledon mitogenome. We sequenced and assembled the complete mitogenome of A. shenzhenica, resulting in a circular mitochondrial draft of 672,872 bp, with an average read coverage of 122× and a GC content of 44.4%. A. shenzhenica mitogenome contained 36 protein-coding genes, 16 tRNAs, two rRNAs, and two copies of nad4L. Repeat sequence analysis revealed a large number of medium and small repeats, accounting for 1.28% of the mitogenome sequence. Selection pressure analysis indicated high mitogenome conservation in related species. RNA editing identified 416 sites in the protein-coding region. Furthermore, we found 44 chloroplast genomic DNA fragments that were transferred from the chloroplast to the mitogenome of A. shenzhenica, with five plastid-derived genes remaining intact in the mitogenome. Finally, the phylogenetic analysis of the mitogenomes from A. shenzhenica and 28 other monocots showed that the evolution and classification of most monocots were well determined. These findings enrich the genetic resources of orchids and provide valuable information on the taxonomic classification and molecular evolution of monocots.}, } @article {pmid37171259, year = {2023}, author = {Dowling, DK and Wolff, JN}, title = {Evolutionary genetics of the mitochondrial genome: insights from Drosophila.}, journal = {Genetics}, volume = {}, number = {}, pages = {}, doi = {10.1093/genetics/iyad036}, pmid = {37171259}, issn = {1943-2631}, abstract = {Mitochondria are key to energy conversion in virtually all eukaryotes. Intriguingly, despite billions of years of evolution inside the eukaryote, mitochondria have retained their own small set of genes involved in the regulation of oxidative phosphorylation (OXPHOS) and protein translation. Although there was a long-standing assumption that the genetic variation found within the mitochondria would be selectively neutral, research over the past 3 decades has challenged this assumption. This research has provided novel insight into the genetic and evolutionary forces that shape mitochondrial evolution and broader implications for evolutionary ecological processes. Many of the seminal studies in this field, from the inception of the research field to current studies, have been conducted using Drosophila flies, thus establishing the species as a model system for studies in mitochondrial evolutionary biology. In this review, we comprehensively review these studies, from those focusing on genetic processes shaping evolution within the mitochondrial genome, to those examining the evolutionary implications of interactions between genes spanning mitochondrial and nuclear genomes, and to those investigating the dynamics of mitochondrial heteroplasmy. We synthesize the contribution of these studies to shaping our understanding of the evolutionary and ecological implications of mitochondrial genetic variation.}, } @article {pmid37166639, year = {2023}, author = {Maiti, P and Fontanesi, F}, title = {Metabolic Labeling of Mitochondrial Translation Products in Whole Cells and Isolated Organelles.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2661}, number = {}, pages = {193-215}, pmid = {37166639}, issn = {1940-6029}, abstract = {Mitochondria retain their own genome and translational apparatus that is highly specialized in the synthesis of a handful of proteins, essential components of the oxidative phosphorylation system. During evolution, the players and mechanisms involved in mitochondrial translation have acquired some unique features, which we have only partially disclosed. The study of the mitochondrial translation process has been historically hampered by the lack of an in vitro translational system and has largely relied on the analysis of the incorporation rate of radiolabeled amino acids into mitochondrial proteins in cellulo or in organello. In this chapter, we describe methods to monitor mitochondrial translation by labeling newly synthesized mitochondrial polypeptides with [S[35]]-methionine in either yeast or mammalian whole cells or isolated mitochondria.}, } @article {pmid37166631, year = {2023}, author = {Chrzanowska-Lightowlers, ZM and Lightowlers, RN}, title = {Translation in Mitochondrial Ribosomes.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2661}, number = {}, pages = {53-72}, pmid = {37166631}, issn = {1940-6029}, abstract = {Mitochondrial protein synthesis is essential for the life of aerobic eukaryotes. Without it, oxidative phosphorylation cannot be coupled. Evolution has shaped a battery of factors and machinery that are key to production of just a handful of critical proteins. In this general concept chapter, we attempt to briefly summarize our current knowledge of the overall process in mitochondria from a variety of species, breaking this down to the four parts of translation: initiation, elongation, termination, and recycling. Where appropriate, we highlight differences between species and emphasize gaps in our understanding. Excitingly, with the current revolution in cryoelectron microscopy and mitochondrial genome editing, it is highly likely that many of these gaps will be resolved in the near future. However, the absence of a faithful in vitro reconstituted system to study mitochondrial translation is still problematic.}, } @article {pmid37166629, year = {2023}, author = {Agrawal, RK and Majumdar, S}, title = {Evolution: Mitochondrial Ribosomes Across Species.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2661}, number = {}, pages = {7-21}, pmid = {37166629}, issn = {1940-6029}, abstract = {The ribosome is among the most complex and ancient cellular macromolecular assemblies that plays a central role in protein biosynthesis in all living cells. Its function of translation of genetic information encoded in messenger RNA into protein molecules also extends to subcellular compartments in eukaryotic cells such as apicoplasts, chloroplasts, and mitochondria. The origin of mitochondria is primarily attributed to an early endosymbiotic event between an alpha-proteobacterium and a primitive (archaeal) eukaryotic cell. The timeline of mitochondrial acquisition, the nature of the host, and their diversification have been studied in great detail and are continually being revised as more genomic and structural data emerge. Recent advancements in high-resolution cryo-EM structure determination have provided architectural details of mitochondrial ribosomes (mitoribosomes) from various species, revealing unprecedented diversifications among them. These structures provide novel insights into the evolution of mitoribosomal structure and function. Here, we present a brief overview of the existing mitoribosomal structures in the context of the eukaryotic evolution tree showing their diversification from their last common ancestor.}, } @article {pmid37162347, year = {2023}, author = {Ezawa, T and Silvestri, A and Maruyama, H and Tawaraya, K and Suzuki, M and Duan, Y and Turina, M and Lanfranco, L}, title = {Structurally distinct mitoviruses: are they an ancestral lineage of the Mitoviridae exclusive to arbuscular mycorrhizal fungi (Glomeromycotina)?.}, journal = {mBio}, volume = {}, number = {}, pages = {e0024023}, doi = {10.1128/mbio.00240-23}, pmid = {37162347}, issn = {2150-7511}, abstract = {Mitoviruses in the family Mitoviridae are the mitochondria-replicating "naked RNA viruses" with genomes encoding only the replicase RNA-dependent RNA polymerase (RdRp) and prevalent across fungi, plants, and invertebrates. Arbuscular mycorrhizal fungi in the subphylum Glomeromycotina are obligate plant symbionts that deliver water and nutrients to the host. We discovered distinct mitoviruses in glomeromycotinian fungi, namely "large duamitovirus," encoding unusually large RdRp with a unique N-terminal motif that is endogenized in some host genomes. More than 400 viral sequences similar to the large duamitoviruses are present in metatranscriptome databases. They are globally distributed in soil ecosystems, consistent with the cosmopolitan distribution of glomeromycotinian fungi, and formed the most basal clade of the Mitoviridae in phylogenetic analysis. Given that glomeromycotinian fungi are the only confirmed hosts of these viruses, we propose the hypothesis that large duamitoviruses are the most ancestral lineage of the Mitoviridae that have been maintained exclusively in glomeromycotinian fungi.}, } @article {pmid37158879, year = {2023}, author = {Shamanskiy, V and Mikhailova, AA and Tretiakov, EO and Ushakova, K and Mikhailova, AG and Oreshkov, S and Knorre, DA and Ree, N and Overdevest, JB and Lukowski, SW and Gostimskaya, I and Yurov, V and Liou, CW and Lin, TK and Kunz, WS and Reymond, A and Mazunin, I and Bazykin, GA and Fellay, J and Tanaka, M and Khrapko, K and Gunbin, K and Popadin, K}, title = {Secondary structure of the human mitochondrial genome affects formation of deletions.}, journal = {BMC biology}, volume = {21}, number = {1}, pages = {103}, pmid = {37158879}, issn = {1741-7007}, mesh = {Animals ; Humans ; *Genome, Mitochondrial ; Mitochondria ; DNA, Mitochondrial/genetics ; Genome, Human ; Protein Structure, Secondary ; DNA, Single-Stranded ; Mammals ; }, abstract = {BACKGROUND: Aging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Such deletions are often flanked by direct nucleotide repeats, but this alone does not fully explain their distribution. Here, we hypothesized that the close proximity of direct repeats on single-stranded mitochondrial DNA (mtDNA) might play a role in the formation of deletions.

RESULTS: By analyzing human mtDNA deletions in the major arc of mtDNA, which is single-stranded during replication and is characterized by a high number of deletions, we found a non-uniform distribution with a "hot spot" where one deletion breakpoint occurred within the region of 6-9 kb and another within 13-16 kb of the mtDNA. This distribution was not explained by the presence of direct repeats, suggesting that other factors, such as the spatial proximity of these two regions, can be the cause. In silico analyses revealed that the single-stranded major arc may be organized as a large-scale hairpin-like loop with a center close to 11 kb and contacting regions between 6-9 kb and 13-16 kb, which would explain the high deletion activity in this contact zone. The direct repeats located within the contact zone, such as the well-known common repeat with a first arm at 8470-8482 bp (base pair) and a second arm at 13,447-13,459 bp, are three times more likely to cause deletions compared to direct repeats located outside of the contact zone. A comparison of age- and disease-associated deletions demonstrated that the contact zone plays a crucial role in explaining the age-associated deletions, emphasizing its importance in the rate of healthy aging.

CONCLUSIONS: Overall, we provide topological insights into the mechanism of age-associated deletion formation in human mtDNA, which could be used to predict somatic deletion burden and maximum lifespan in different human haplogroups and mammalian species.}, } @article {pmid37153218, year = {2023}, author = {Xu, J and Li, B and Jiang, Z and Wang, W and Yang, Y and Yang, M and Ye, X}, title = {Genomic analyses provide insights into the genome evolution and environmental adaptation of the tobacco moth Ephestia elutella.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1187522}, pmid = {37153218}, issn = {1664-042X}, abstract = {Ephestia elutella is a major pest responsible for significant damage to stored tobacco over many years. Here, we conduct a comparative genomic analysis on this pest, aiming to explore the genetic bases of environmental adaptation of this species. We find gene families associated with nutrient metabolism, detoxification, antioxidant defense and gustatory receptors are expanded in the E. elutella genome. Detailed phylogenetic analysis of P450 genes further reveals obvious duplications in the CYP3 clan in E. elutella compared to the closely related species, the Indianmeal moth Plodia interpunctella. We also identify 229 rapidly evolving genes and 207 positively selected genes in E. elutella, respectively, and highlight two positively selected heat shock protein 40 (Hsp40) genes. In addition, we find a number of species-specific genes related to diverse biological processes, such as mitochondria biology and development. These findings advance our understanding of the mechanisms underlying processes of environmental adaptation on E. elutella and will enable the development of novel pest management strategies.}, } @article {pmid37152468, year = {2023}, author = {Kannan, B and Arumugam, P}, title = {The implication of mitochondrial DNA mutation and dysfunction in periodontal diseases.}, journal = {Journal of Indian Society of Periodontology}, volume = {27}, number = {2}, pages = {126-130}, pmid = {37152468}, issn = {0972-124X}, abstract = {Periodontitis is a chronic oral inflammatory disease that is caused by dental plaque pathogens. Periodontal disease development and evolution are based on the host immune system, humoral and cellular immunity, the integrity of the tissues, and certain endocrine and nutritional factors. Mitochondria are significantly involved in periodontal infections and inflammation, which play a role in the inflammatory response in a variety of ways. In general, oxidative stress causes a stressful environment that subsequently leads to tissue damage and chronic inflammation. Several mutations and alterations in mitochondrial DNA lead the disease to an aggressive condition, by causing dysregulated mitochondrial function. Such mutations are significantly associated with various diseases. Numerous studies indicate chronic periodontitis patients have a decreased level of mitochondrial membrane potential, as well as adenosine triphosphate, and an increased level of reactive oxygen species production, which causes cell death in the periodontium and affects tissue growth. Further studies into the association between mitochondria and periodontitis might be helpful for the treatment and prevention of the diseases.}, } @article {pmid37141262, year = {2023}, author = {Squires, TE and Rödin-Mörch, P and Formenti, G and Tracey, A and Abueg, L and Brajuka, N and Jarvis, E and Halapi, EC and Melsted, P and Höglund, J and Magnússon, KP}, title = {A Chromosome-Level Genome Assembly for the Rock Ptarmigan (Lagopus muta).}, journal = {G3 (Bethesda, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1093/g3journal/jkad099}, pmid = {37141262}, issn = {2160-1836}, abstract = {The Rock Ptarmigan (Lagopus muta) is a cold-adapted, largely sedentary, game bird with a Holarctic distribution. The species represents an important example of an organism likely to be affected by ongoing climatic shifts across a disparate range. We provide here a high-quality reference genome and mitogenome for the Rock Ptarmigan assembled from PacBio HiFi and Hi-C sequencing of a female bird from Iceland. The total size of the genome is 1.03 Gb with a scaffold N50 of 71.23 Mb and a contig N50 of 17.91 Mb. The final scaffolds represent all 40 predicted chromosomes, and the mitochondria with a BUSCO score of 98.6%. Gene annotation resulted in 16,078 protein-coding genes out of a total 19,831 predicted (81.08% excluding pseudogenes). The genome included 21.07% repeat sequences, and the average length of genes, exons, and introns were, 33605, 394, and 4265 bp respectively. The availability of a new reference-quality genome will contribute to understanding the Rock Ptarmigan's unique evolutionary history, vulnerability to climate change, and demographic trajectories around the globe while serving as a benchmark for species in the family Phasianidae (order Galliformes).}, } @article {pmid36944856, year = {2023}, author = {Niedziałkowska, M and Tarnowska, E and Babik, W and Konczal, M and Gharbi, K and Cezard, T and Jędrzejewska, B}, title = {Different waves of postglacial recolonisation and genomic structure of bank vole populations in NE Poland.}, journal = {Heredity}, volume = {130}, number = {5}, pages = {269-277}, pmid = {36944856}, issn = {1365-2540}, mesh = {Humans ; Animals ; Poland ; Phylogeny ; *DNA, Mitochondrial/genetics ; *Genomics ; Arvicolinae/genetics ; Genetic Variation ; }, abstract = {Previous studies indicated that in some species phylogeographic patterns obtained in the analysis of nuclear and mitochondrial DNA (mtDNA) markers can be different. Such mitonuclear discordance can have important evolutionary and ecological consequences. In the present study, we aimed to check whether there was any discordance between mtDNA and nuclear DNA in the bank vole population in the contact zone of its two mtDNA lineages. We analysed the population genetic structure of bank voles using genome-wide genetic data (SNPs) and diversity of sequenced heart transcriptomes obtained from selected individuals from three populations inhabiting areas outside the contact zone. The SNP genetic structure of the populations confirmed the presence of at least two genetic clusters, and such division was concordant with the patterns obtained in the analysis of other genetic markers and functional genes. However, genome-wide SNP analyses revealed the more detailed structure of the studied population, consistent with more than two bank vole recolonisation waves, as recognised previously in the study area. We did not find any significant differences between individuals representing two separate mtDNA lineages of the species in functional genes coding for protein-forming complexes, which are involved in the process of cell respiration in mitochondria. We concluded that the contemporary genetic structure of the populations and the width of the contact zone were shaped by climatic and environmental factors rather than by genetic barriers. The studied populations were likely isolated in separate Last Glacial Maximum refugia for insufficient amount of time to develop significant genetic differentiation.}, } @article {pmid37126705, year = {2023}, author = {Espino-Sanchez, TJ and Wienkers, H and Marvin, RG and Nalder, SA and García-Guerrero, AE and VanNatta, PE and Jami-Alahmadi, Y and Mixon Blackwell, A and Whitby, FG and Wohlschlegel, JA and Kieber-Emmons, MT and Hill, CP and Sigala, PA}, title = {Direct tests of cytochrome c and c1 functions in the electron transport chain of malaria parasites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {19}, pages = {e2301047120}, doi = {10.1073/pnas.2301047120}, pmid = {37126705}, issn = {1091-6490}, support = {T32 DK007115/DK/NIDDK NIH HHS/United States ; R25 HL108828/HL/NHLBI NIH HHS/United States ; U54 DK110858/DK/NIDDK NIH HHS/United States ; R35 GM133764/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cytochromes c ; Electron Transport ; *Parasites ; *Antimalarials ; *Malaria, Falciparum ; Eukaryota ; Cytochromes c1 ; }, abstract = {The mitochondrial electron transport chain (ETC) of Plasmodium malaria parasites is a major antimalarial drug target, but critical cytochrome (cyt) functions remain unstudied and enigmatic. Parasites express two distinct cyt c homologs (c and c-2) with unusually sparse sequence identity and uncertain fitness contributions. P. falciparum cyt c-2 is the most divergent eukaryotic cyt c homolog currently known and has sequence features predicted to be incompatible with canonical ETC function. We tagged both cyt c homologs and the related cyt c1 for inducible knockdown. Translational repression of cyt c and cyt c1 was lethal to parasites, which died from ETC dysfunction and impaired ubiquinone recycling. In contrast, cyt c-2 knockdown or knockout had little impact on blood-stage growth, indicating that parasites rely fully on the more conserved cyt c for ETC function. Biochemical and structural studies revealed that both cyt c and c-2 are hemylated by holocytochrome c synthase, but UV-vis absorbance and EPR spectra strongly suggest that cyt c-2 has an unusually open active site in which heme is stably coordinated by only a single axial amino acid ligand and can bind exogenous small molecules. These studies provide a direct dissection of cytochrome functions in the ETC of malaria parasites and identify a highly divergent Plasmodium cytochrome c with molecular adaptations that defy a conserved role in eukaryotic evolution.}, } @article {pmid37116483, year = {2023}, author = {George, EE and Barcytė, D and Lax, G and Livingston, S and Tashyreva, D and Husnik, F and Lukeš, J and Eliáš, M and Keeling, PJ}, title = {A single cryptomonad cell harbors a complex community of organelles, bacteria, a phage, and selfish elements.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2023.04.010}, pmid = {37116483}, issn = {1879-0445}, abstract = {Symbiosis between prokaryotes and microbial eukaryotes (protists) has broadly impacted both evolution and ecology. Endosymbiosis led to mitochondria and plastids, the latter spreading across the tree of eukaryotes by subsequent rounds of endosymbiosis. Present-day endosymbionts in protists remain both common and diverse, although what function they serve is often unknown. Here, we describe a highly complex community of endosymbionts and a bacteriophage (phage) within a single cryptomonad cell. Cryptomonads are a model for organelle evolution because their secondary plastid retains a relict endosymbiont nucleus, but only one previously unidentified Cryptomonas strain (SAG 25.80) is known to harbor bacterial endosymbionts. We carried out electron microscopy and FISH imaging as well as genomic sequencing on Cryptomonas SAG 25.80, which revealed a stable, complex community even after over 50 years in continuous cultivation. We identified the host strain as Cryptomonas gyropyrenoidosa, and sequenced genomes from its mitochondria, plastid, and nucleomorph (and partially its nucleus), as well as two symbionts, Megaira polyxenophila and Grellia numerosa, and one phage (MAnkyphage) infecting M. polyxenophila. Comparing closely related endosymbionts from other hosts revealed similar metabolic and genomic features, with the exception of abundant transposons and genome plasticity in M. polyxenophila from Cryptomonas. We found an abundance of eukaryote-interacting genes as well as many toxin-antitoxin systems, including in the MAnkyphage genome that also encodes several eukaryotic-like proteins. Overall, the Cryptomonas cell is an endosymbiotic conglomeration with seven distinct evolving genomes that all show evidence of inter-lineage conflict but nevertheless remain stable, even after more than 4,000 generations in culture.}, } @article {pmid37115919, year = {2023}, author = {Al Jewari, C and Baldauf, SL}, title = {An excavate root for the eukaryote tree of life.}, journal = {Science advances}, volume = {9}, number = {17}, pages = {eade4973}, pmid = {37115919}, issn = {2375-2548}, mesh = {*Eukaryota/genetics ; *Eukaryotic Cells ; Biological Evolution ; Phylogeny ; Evolution, Molecular ; }, abstract = {Much of the higher-order phylogeny of eukaryotes is well resolved, but the root remains elusive. We assembled a dataset of 183 eukaryotic proteins of archaeal ancestry to test this root. The resulting phylogeny identifies four lineages of eukaryotes currently classified as "Excavata" branching separately at the base of the tree. Thus, Parabasalia appear as the first major branch of eukaryotes followed sequentially by Fornicata, Preaxostyla, and Discoba. All four excavate branch points receive full statistical support from analyses with commonly used evolutionary models, a protein structure partition model that we introduce here, and various controls for deep phylogeny artifacts. The absence of aerobic mitochondria in Parabasalia, Fornicata, and Preaxostyla suggests that modern eukaryotes arose under anoxic conditions, probably much earlier than expected, and without the benefit of mitochondrial respiration.}, } @article {pmid37107542, year = {2023}, author = {De, AK and Sawhney, S and Sunder, J and Muthiyan, R and Ponraj, P and Sujatha, T and Malakar, D and Mondal, S and Bera, AK and Kumar, A and Chakurkar, EB and Bhattacharya, D}, title = {Peeping into Mitochondrial Diversity of Andaman Goats: Unveils Possibility of Maritime Transport with Diversified Geographic Signaling.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, pmid = {37107542}, issn = {2073-4425}, mesh = {Animals ; Cattle ; Swine ; *Goats/genetics ; Phylogeny ; *DNA, Mitochondrial/genetics ; Sequence Analysis, DNA ; Mitochondria/genetics ; }, abstract = {Andaman and Nicobar Islands, a part of South-East Asia, is enriched with the presence of native breeds of livestock (cattle, pig, goat) and poultry. There are two native goat breeds, viz., Andaman local goat and Teressa goat in Andaman and Nicobar Islands. However, to date, the origin and genetic makeup of these two breeds have not been detailed. Therefore, the present study describes the genetic makeup of Andaman goats through analysis of mitochondrial D-loop sequence for sequence polymorphism, phylogeographical signaling and population expansion events. The genetic diversity of the Teressa goat was less compared to the Andaman local goat due to its sole presence on Teressa Island. Out of 38 well-defined haplotypes of Andaman goats, the majority of haplotypes belonged to haplogroup A followed by haplogroup B and haplogroup D. The result of mismatch distribution and neutrality tests indicated no population expansion event of haplogroup A and B. Finally, based on poor geographical signaling, we hypothesize that Andaman goats have been imported to these Islands either through multidirectional diffusion or unidirectional diffusion. We justify our hypothesis of multidirectional diffusion on the basis of observation of the haplotype and nucleotide diversity of Andaman goats. Simultaneously, the probability of unidirectional diffusion of goats in these islands from the Indian subcontinent in different spells of domestication events through maritime routes cannot be ignored.}, } @article {pmid36877343, year = {2023}, author = {Palacios-Barreto, P and Mar-Silva, AF and Bayona-Vasquez, NJ and Adams, DH and Díaz-Jaimes, P}, title = {Characterization of the complete mitochondrial genome of the brazilian cownose ray Rhinoptera brasiliensis (Myliobatiformes, Rhinopteridae) in the western Atlantic and its phylogenetic implications.}, journal = {Molecular biology reports}, volume = {50}, number = {5}, pages = {4083-4095}, pmid = {36877343}, issn = {1573-4978}, mesh = {Animals ; Phylogeny ; *Genome, Mitochondrial/genetics ; Brazil ; DNA, Mitochondrial/genetics ; *Skates, Fish/genetics ; Codon, Terminator ; RNA, Transfer/genetics ; }, abstract = {BACKGROUND: The Brazilian cownose ray, Rhinoptera brasiliensis has undergone a global population reduction and is currently classified by IUCN as Vulnerable. This species is sometimes confused with Rhinoptera bonasus, the only external diagnostic characteristic to distinguish between both species is the number of rows of tooth plates. Both cownose rays overlap geographically from Rio de Janeiro to the western North Atlantic. This calls for a more comprehensive phylogenetic assessment using mitochondria DNA genomes to better understand the relationships and delimitation of these two species.

METHODS AND RESULTS: The mitochondrial genome sequences of R. brasiliensis was obtained by next-generation sequencing. The length of the mitochondrial genome was 17,759 bp containing 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a non-coding control region (D-loop). Each PCG was initiated by an authoritative ATG codon, except for COX1 initiated by a GTG codon. Most of the PCGs were terminated by a complete codon (TAA/TAG), while an incomplete termination codon (TA/T) was found in five out of the 13 PCGs. The phylogenetic analysis showed that R. brasiliensis was closely related to R. steindachneri whereas the reported mitogenome as R. steindachneri (GenBank accession number KM364982), differs from multiple mitocondrial DNA sequences of R. steindachneri and is nearly identical to that of R. javanica.

CONCLUSION: The new mitogenome determined in this study provides new insight into the phylogenetic relationships in Rhinoptera, while providing new molecular data that can be applied to population genetic studies.}, } @article {pmid37113597, year = {2023}, author = {Mahati, K and Padmasree, K}, title = {Brassinolide promotes interaction between chloroplasts and mitochondria during the optimization of photosynthesis by the mitochondrial electron transport chain in mesophyll cell protoplasts of Arabidopsis thaliana.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1099474}, pmid = {37113597}, issn = {1664-462X}, abstract = {The current experimental data unveils the role of brassinolide (BL), a phytohormone of class brassinosteroids (BRs), in augmenting the cross-talk between the mitochondrial electron transport chain (mETC) and chloroplasts to strengthen the efficiency of the Calvin-Benson cycle (CBC) for higher assimilation of carbon dioxide in the mesophyll cell protoplasts (MCP) of Arabidopsis thaliana. The outcome of total respiration (TR) and photosynthetic carbon assimilation (PCA) was monitored as O2 uptake under dark and NaHCO3-dependent O2 evolution under light, respectively, after pre-incubation of MCP at a broad spectrum of BL concentration from 0.05 pM to 5 pM at 25 °C and optimum light intensity of 1000 μmol m[-2] s[-1]. The addition of optimal concentration (0.5 pM) of BL to MCP stimulated the (i) TR, (ii) PCA, and (iii) para-benzoquinone-dependent O2 evolution (PSII activity). Further, in response to BL, the enzyme activity or transcript levels of redox-regulated CBC enzymes and glucose-6-phosphate raised considerably. Also, the addition of BL to MCP remarkably accelerated the capacity of the cytochrome oxidase (COX) and alternative oxidase (AOX) pathways concurrently with an increase in total cellular pyruvate and reactive oxygen species (ROS) levels. Besides, malate valve components (Malate, Chl-MDH, M-MDH) increased in response to BL. At the same time, the cellular redox ratios of pyridine nucleotides (NADPH and NADH) were kept low in the presence of BL. However, BL could not keep up the CBC activity of photosynthesis along with its associated light-activated enzymes/transcripts when mETC through COX or AOX pathway is restricted by antimycin A (AA) or salicylhydroxamic acid (SHAM), respectively. In contrast, adding BL to MCP under restricted mETC showed aggravation in total cellular ROS, pyruvate, malate, and redox ratio of pyridine nucleotides with a concomitant increase in transcripts associated with malate valve and antioxidant systems. These results suggest that BL enhances the PCA by coordinating in cross-talk of chloroplasts and mitochondria to regulate the cellular redox ratio or ROS through the involvement of COX and AOX pathways along with the malate valve and antioxidant systems.}, } @article {pmid37107622, year = {2023}, author = {Li, X and Zhe, M and Huang, Y and Fan, W and Yang, J and Zhu, A}, title = {The Evolution of Mitochondrial Genomes between Two Cymbidium Sister Species: Dozens of Circular Chromosomes and the Maintenance and Deterioration of Genome Synteny.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/genes14040864}, pmid = {37107622}, issn = {2073-4425}, abstract = {Plant mitochondrial genomes (mitogenomes) exhibit fluid genome architectures, which could lead to the rapid erosion of genome synteny over a short evolutionary time scale. Among the species-rich orchid family, the leafy Cymbidium lancifolium and leafless Cymbidium macrorhizon are sister species with remarkable differences in morphology and nutritional physiology. Although our understanding of the evolution of mitochondria is incomplete, these sister taxa are ideal for examining this subject. In this study, the complete mitogenomes of C. lancifolium and C. macrorhizon, totaling 704,244 bp and 650,751 bp, respectively, were assembled. In the 2 mitogenomes, 38 protein-coding genes, 18 cis- and 6 trans-spliced introns, and approximately 611 Kb of homologous sequences are identical; overall, they have 99.4% genome-wide similarity. Slight variations in the mitogenomes of C. lancifolium and C. macrorhizon in repeat content (21.0 Kb and 21.6 Kb, respectively) and mitochondrial DNA of plastid origin (MIPT; 38.2 Kb and 37.5 Kb, respectively) were observed. The mitogenome architectures of C. lancifolium and C. macrorhizon are complex and comprise 23 and 22 mini-circular chromosomes, respectively. Pairwise comparisons indicate that the two mitogenomes are largely syntenic, and the disparity in chromosome numbers is likely due to repeat-mediated rearrangements among different chromosomes. Notably, approximately 93.2 Kb C. lancifolium mitochondrial sequences lack any homology in the C. macrorhizon mitogenome, indicating frequent DNA gains and losses, which accounts mainly for the size variation. Our findings provide unique insights into mitogenome evolution in leafy and leafless plants of sister species and shed light on mitogenome dynamics during the transition from mixotrophy to mycoheterotrophy.}, } @article {pmid37082671, year = {2023}, author = {Ibodeng, GO and Uche, IN and Mokua, R and Galo, M and Odigwe, B and Galeas, JN and Dasgupta, S}, title = {A snapshot of lung cancer: where are we now?-a narrative review.}, journal = {Annals of translational medicine}, volume = {11}, number = {6}, pages = {261}, pmid = {37082671}, issn = {2305-5839}, abstract = {BACKGROUND AND OBJECTIVE: The global impact of cancer and cancer-related deaths has been a huge challenge and continues to be a setback in the health sector and beyond even in recent times. Cancer is the second leading cause of death globally with lung cancer (LC) being the second most prevalent malignancy and the leading cause of mortality amongst cancers in men and women worldwide. LC still constitutes a major burden despite recent advances in diagnostic and treatment tools. In this article, we review the trends in LC with an emphasis on non-small cell LC. We aimed to identify nuclear and mitochondrial genetic alterations, microbiome dysbiosis, and their significance in non-small cell LC tumorigenesis as well as its relevance in the future management of LCs.

METHODS: We identified studies for this review by searching the PubMed, Cochrane, Education Resources Information Center (ERIC), and Surveillance, Epidemiology, and End Results (SEER) databases for English-Language articles published from January 1, 2000 through to July 30, 2022, using keywords: lung cancer, non-small cell lung cancer, early detection, treatment, mitochondria, microbiome and epigenetics.

KEY CONTENT AND FINDINGS: This review will highlight the genomic environment, mitochondrial and nuclear alterations that play a role in the etiopathogenesis of LC and its application in the progression as well as management of the disease. We also elaborate on current molecular tumor biomarkers and their therapeutic targets.

CONCLUSIONS: LC remains the leading cause of cancer-related deaths globally with poor prognosis despite available treatment options and even recent advances in both diagnostic tools and management guidelines. Human nuclear and mitochondrial alterations clearly play a role in tumorigenesis and progressive genomic evolution is crucial in the early carcinogenesis of LC which is strongly influenced by host immune surveillance. It is imperative that more research and clinical trials be undertaken to appreciate an in-depth understanding of LC from the molecular level to facilitate the discovery of more targeted therapy and overall better management of LC.}, } @article {pmid36972795, year = {2023}, author = {Benites, P and Zaldívar-Riverón, A and Meza-Lázaro, RN and Samacá-Sáenz, E and Gutiérrez-Rodríguez, J and Hernández-López, A}, title = {Multiple introgression events during the diversification history of the edible Mexican grasshopper genus Sphenarium (Orthoptera: Pyrgomorphidae).}, journal = {Molecular phylogenetics and evolution}, volume = {183}, number = {}, pages = {107774}, doi = {10.1016/j.ympev.2023.107774}, pmid = {36972795}, issn = {1095-9513}, mesh = {Animals ; Phylogeny ; *Grasshoppers/genetics ; Mexico ; DNA, Mitochondrial/genetics/chemistry ; Mitochondria/genetics ; }, abstract = {Speciation with gene flow often leads to ambiguous phylogenetic reconstructions, reticulate patterns of relatedness and conflicting nuclear versus mitochondrial (mt) lineages. Here we employed a fragment of the COI mtDNA gene and nuclear genome-wide data (3RAD) to assess the diversification history of Sphenarium, an orthopteran genus of great economic importance in Mexico that is presumed to have experienced hybridisation events in some of its species. We carried out separate phylogenetic analyses to evaluate the existence of mito-nuclear discordance in the species relationships, and also assessed the genomic diversity and population genomic structure and investigated the existence of interspecific introgression and species limits of the taxa involved based on the nuclear dataset. The species delineation analyses discriminated all the currently recognised species, but also supported the existence of four undescribed species. The mt and nuclear topologies had four discordant species relationships that can be explained by mt introgression, where the mt haplotypes of S. purpurascens appear to have replaced those of S. purpurascens A and B, S. variabile and S. zapotecum. Moreover, our analyses supported the existence of nuclear introgression events between four species pairs that are distributed in the Sierra Madre del Sur province in southeast Mexico, with three of them occurring in the Tehuantepec Isthmus region. Our study highlights the relevance of genomic data to address the relative importance of allopatric isolation versus gene flow in speciation.}, } @article {pmid36893930, year = {2023}, author = {Jesus, PB and Lyra, GM and Zhang, H and Fujii, MT and Nauer, F and Nunes, JMC and Davis, CC and Oliveira, MC}, title = {Phylogenomics and taxon-rich phylogenies of new and historical specimens shed light on the systematics of Hypnea (Cystocloniaceae, Rhodophyta).}, journal = {Molecular phylogenetics and evolution}, volume = {183}, number = {}, pages = {107752}, doi = {10.1016/j.ympev.2023.107752}, pmid = {36893930}, issn = {1095-9513}, mesh = {Phylogeny ; *Rhodophyta/genetics ; Organelles ; Mitochondria ; Chloroplasts ; }, abstract = {Cystocloniacae is a highly diverse family of Rhodophyta, including species of ecological and economic importance, whose phylogeny remains largely unresolved. Species delimitation is unclear, particularly in the most speciose genus, Hypnea, and cryptic diversity has been revealed by recent molecular assessments, especially in the tropics. Here, we carried out the first phylogenomic investigation of Cystocloniaceae, focused on the genus Hypnea, inferred from chloroplast and mitochondrial genomes including taxa sampled from new and historical collections. In this work, molecular synapomorphies (gene losses, InDels and gene inversions) were identified to better characterize clades in our congruent organellar phylogenies. We also present taxon-rich phylogenies based on plastid and mitochondrial markers. Molecular and morphological comparisons of historic collections with contemporary specimens revealed the need for taxonomic updates in Hypnea, the synonymization of H. marchantiae to a later heterotypic synonym of H. cervicornis and the description of three new species: H. davisiana sp. nov., H. djamilae sp. nov. and H. evaristoae sp. nov.}, } @article {pmid36727263, year = {2023}, author = {Blair, C}, title = {Organellar DNA continues to provide a rich source of information in the genomics era.}, journal = {Molecular ecology}, volume = {32}, number = {9}, pages = {2144-2150}, doi = {10.1111/mec.16872}, pmid = {36727263}, issn = {1365-294X}, mesh = {Phylogeny ; *Information Sources ; *DNA, Mitochondrial/genetics ; Genomics ; Mitochondria/genetics ; DNA, Chloroplast/genetics ; Sequence Analysis, DNA ; }, abstract = {The genomics revolution continues to change how ecologists and evolutionary biologists study the evolution and maintenance of biodiversity. It is now easier than ever to generate large molecular data sets consisting of hundreds to thousands of independently evolving nuclear loci to estimate a suite of evolutionary and demographic parameters. However, any inferences will be incomplete or inaccurate if incorrect taxonomic identities and perpetuated throughout the analytical pipeline. Due to decades of research and comprehensive online databases, sequencing and analysis of mitochondrial DNA (mtDNA), chloroplast DNA (cpDNA) and select nuclear genes can provide researchers with a cost effective and simple means to verify the species identity of samples prior to subsequent phylogeographic and population genomic analysis. The addition of these sequences to genomic studies can also shed light on other important evolutionary questions such as explanations for gene tree-species tree discordance, species limits, sex-biased dispersal patterns, adaptation, and mtDNA introgression. Although the mtDNA and cpDNA genomes often should not be used exclusively to make historical inferences given their well-known limitations, the addition of these data to modern genomic studies adds little cost and effort while simultaneously providing a wealth of useful data that can have significant implications for both basic and applied research.}, } @article {pmid37077029, year = {2023}, author = {Park, D and Yu, Y and Kim, JH and Lee, J and Park, J and Hong, K and Seo, JK and Lim, C and Min, KT}, title = {Suboptimal Mitochondrial Activity Facilitates Nuclear Heat Shock Responses for Proteostasis and Genome Stability.}, journal = {Molecules and cells}, volume = {}, number = {}, pages = {}, doi = {10.14348/molcells.2023.2181}, pmid = {37077029}, issn = {0219-1032}, abstract = {Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pathways. Mitochondrial ribosomal protein (MRP) depletion enhanced the nucleolar granule formation of HSP70 and ubiquitin during HSR while facilitating the recovery of damaged nuclear proteins and impaired nucleocytoplasmic transport. Treatment of the mitochondrial proton gradient uncoupler masked MRP-depletion effects, implicating oxidative phosphorylation in these nuclear HSRs. On the other hand, MRP depletion and a reactive oxygen species (ROS) scavenger non-additively decreased mitochondrial ROS generation during HSR, thereby protecting the nuclear genome from DNA damage. These results suggest that suboptimal mitochondrial activity sustains nuclear homeostasis under cellular stress, providing plausible evidence for optimal endosymbiotic evolution via mitochondria-to-nuclear communication.}, } @article {pmid37074804, year = {2023}, author = {McGuire, JA and Huang, X and Reilly, SB and Iskandar, DT and Wang-Claypool, C and Werning, S and Chong, RA and Lawalata, SZS and Stubbs, AL and Frederick, JH and Brown, RM and Evans, BJ and Arifin, U and Riyanto, A and Hamidy, A and Arida, E and Koo, MS and Supriatna, J and Andayani, N and Hall, R}, title = {Species Delimitation, Phylogenomics, and Biogeography of Sulawesi Flying Lizards: A Diversification History Complicated by Ancient Hybridization, Cryptic Species, and Arrested Speciation.}, journal = {Systematic biology}, volume = {}, number = {}, pages = {}, doi = {10.1093/sysbio/syad020}, pmid = {37074804}, issn = {1076-836X}, abstract = {The biota of Sulawesi is noted for its high degree of endemism and for its substantial levels of in situ biological diversification. While the island's long period of isolation and dynamic tectonic history have been implicated as drivers of regional diversification, this has rarely been tested in the context of an explicit geological framework. Here we provide a tectonically-informed biogeographical framework that we use to explore the diversification history of Sulawesi flying lizards (the Draco lineatus Group), a radiation that is endemic to Sulawesi and its surrounding islands. We employ a framework for inferring cryptic speciation that involves phylogeographic and genetic clustering analyses as a means of identifying potential species followed by population demographic assessment of divergence-timing and rates of bi-directional migration as means of confirming lineage independence (and thus species status). Using this approach, phylogenetic and population genetic analyses of mitochondrial sequence data obtained for 613 samples, a 50-SNP data set for 370 samples, and a 1249-locus exon-capture data set for 106 samples indicate that the current taxonomy substantially understates the true number of Sulawesi Draco species, that both cryptic and arrested speciation have taken place, and that ancient hybridization confounds phylogenetic analyses that do not explicitly account for reticulation. The Draco lineatus Group appears to comprise 15 species - nine on Sulawesi proper and six on peripheral islands. The common ancestor of this group colonized Sulawesi ~11 Ma when proto-Sulawesi was likely composed of two ancestral islands, and began to radiate ~6 Ma as new islands formed and were colonized via overwater dispersal. The enlargement and amalgamation of many of these proto-islands into modern Sulawesi, especially during the past 3 Ma, set in motion dynamic species interactions as once-isolated lineages came into secondary contact, some of which resulted in lineage merger, and others surviving to the present.}, } @article {pmid37072481, year = {2023}, author = {Christinaki, AC and Theelen, B and Zania, A and Coutinho, SDA and Cabañes, JF and Boekhout, T and Kouvelis, VN}, title = {Co-evolution of large inverted repeats and G-quadruplex DNA in fungal mitochondria may facilitate mitogenome stability: the case of Malassezia.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6308}, pmid = {37072481}, issn = {2045-2322}, abstract = {Mitogenomes are essential due to their contribution to cell respiration. Recently they have also been implicated in fungal pathogenicity mechanisms. Members of the basidiomycetous yeast genus Malassezia are an important fungal component of the human skin microbiome, linked to various skin diseases, bloodstream infections, and they are increasingly implicated in gut diseases and certain cancers. In this study, the comparative analysis of Malassezia mitogenomes contributed to phylogenetic tree construction for all species. The mitogenomes presented significant size and gene order diversity which correlates to their phylogeny. Most importantly, they showed the inclusion of large inverted repeats (LIRs) and G-quadruplex (G4) DNA elements, rendering Malassezia mitogenomes a valuable test case for elucidating the evolutionary mechanisms responsible for this genome diversity. Both LIRs and G4s coexist and convergently evolved to provide genome stability through recombination. This mechanism is common in chloroplasts but, hitherto, rarely found in mitogenomes.}, } @article {pmid37071674, year = {2023}, author = {Libby, E and Kempes, CP and Okie, JG}, title = {Metabolic compatibility and the rarity of prokaryote endosymbioses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {17}, pages = {e2206527120}, doi = {10.1073/pnas.2206527120}, pmid = {37071674}, issn = {1091-6490}, abstract = {The evolution of the mitochondria was a significant event that gave rise to the eukaryotic lineage and most large complex life. Central to the origins of the mitochondria was an endosymbiosis between prokaryotes. Yet, despite the potential benefits that can stem from a prokaryotic endosymbiosis, their modern occurrence is exceptionally rare. While many factors may contribute to their rarity, we lack methods for estimating the extent to which they constrain the appearance of a prokaryotic endosymbiosis. Here, we address this knowledge gap by examining the role of metabolic compatibility between a prokaryotic host and endosymbiont. We use genome-scale metabolic flux models from three different collections (AGORA, KBase, and CarveMe) to assess the viability, fitness, and evolvability of potential prokaryotic endosymbioses. We find that while more than half of host-endosymbiont pairings are metabolically viable, the resulting endosymbioses have reduced growth rates compared to their ancestral metabolisms and are unlikely to gain mutations to overcome these fitness differences. In spite of these challenges, we do find that they may be more robust in the face of environmental perturbations at least in comparison with the ancestral host metabolism lineages. Our results provide a critical set of null models and expectations for understanding the forces that shape the structure of prokaryotic life.}, } @article {pmid37063179, year = {2023}, author = {Tyszka, AS and Bretz, EC and Robertson, HM and Woodcock-Girard, MD and Ramanauskas, K and Larson, DA and Stull, GW and Walker, JF}, title = {Characterizing conflict and congruence of molecular evolution across organellar genome sequences for phylogenetics in land plants.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1125107}, pmid = {37063179}, issn = {1664-462X}, abstract = {Chloroplasts and mitochondria each contain their own genomes, which have historically been and continue to be important sources of information for inferring the phylogenetic relationships among land plants. The organelles are predominantly inherited from the same parent, and therefore should exhibit phylogenetic concordance. In this study, we examine the mitochondrion and chloroplast genomes of 226 land plants to infer the degree of similarity between the organelles' evolutionary histories. Our results show largely concordant topologies are inferred between the organelles, aside from four well-supported conflicting relationships that warrant further investigation. Despite broad patterns of topological concordance, our findings suggest that the chloroplast and mitochondrial genomes evolved with significant differences in molecular evolution. The differences result in the genes from the chloroplast and the mitochondrion preferentially clustering with other genes from their respective organelles by a program that automates selection of evolutionary model partitions for sequence alignments. Further investigation showed that changes in compositional heterogeneity are not always uniform across divergences in the land plant tree of life. These results indicate that although the chloroplast and mitochondrial genomes have coexisted for over 1 billion years, phylogenetically, they are still evolving sufficiently independently to warrant separate models of evolution. As genome sequencing becomes more accessible, research into these organelles' evolution will continue revealing insight into the ancient cellular events that shaped not only their history, but the history of plants as a whole.}, } @article {pmid37045318, year = {2022}, author = {Hasan, ME and Hasan, A and Béarez, P and Shen, KN and Chang, CW and Tran, TTV and Golani, D and Al-Saboonchi, A and Siddiqui, PJA and Durand, JD}, title = {Planiliza lauvergnii (Eydoux & Souleyet, 1850), a senior synonym of Planiliza affinis (Günther, 1861) with a re-evaluation of keeled back mullets&nbsp;(Mugiliformes: Mugilidae).}, journal = {Zootaxa}, volume = {5194}, number = {4}, pages = {497-518}, doi = {10.11646/zootaxa.5194.4.2}, pmid = {37045318}, issn = {1175-5334}, mesh = {Animals ; *Smegmamorpha ; Phylogeny ; Fishes/genetics ; Biological Evolution ; Mitochondria ; }, abstract = {The taxonomic status of the keeled back mullets (Teleostei: Mugilidae) has been reinvestigated. Two nominal mugilid species having keeled backs from East Asia: Mugil lauvergnii Eydoux & Souleyet, 1850 and Mugil affinis Günther, 1861 have been re-evaluated through examination of the holotypes and fresh specimens. Comparison of morpho-meristic characters of the holotypes shows that both species are identical. Phylogenetic analysis based on mitochondrial cytochrome c oxidase 1 (CO1) confirmed morphological data by highlighting presence of a single clade from East Asia. Mugil lauvergnii (=Planiliza lauvergnii) is thus the sole keeled back mullet from East Asia and a senior synonym of Mugil affinis (=Planiliza affinis). The taxonomic status of two other keeled back mullets, Planiliza carinata and P. klunzingeri, is also contentious due to their similar morphology. Meristic and morphometric variation as well as sequence divergence between the two species are limited but phylogenetic analyses delineate well-supported clades consistent with biogeography and currently accepted taxonomy. Planiliza carinata and P. klunzingeri share a recent common ancestor in a Maximum Likelihood tree, with separate distribution ranges while P. lauvergnii formed a paraphyletic lineage. Based on present findings, we suggest maintenance of the taxonomic distinction of P. klunzingeri and P. carinata and discuss its evolutionary significance.}, } @article {pmid37045317, year = {2022}, author = {Opler, PA and Stout, TL and Back, W and Zhang, J and Cong, Q and Shen, J and Grishin, NV}, title = {DNA barcodes reveal different speciation scenarios in the four North American Anthocharis Boisduval, Rambur, [Duménil] & Graslin, [1833] (Lepidoptera: Pieridae: Pierinae: Anthocharidini) species groups.}, journal = {Zootaxa}, volume = {5194}, number = {4}, pages = {519-539}, doi = {10.11646/zootaxa.5194.4.3}, pmid = {37045317}, issn = {1175-5334}, mesh = {Animals ; *DNA Barcoding, Taxonomic ; *Butterflies/genetics ; DNA, Mitochondrial/genetics ; Mitochondria ; Phylogeny ; }, abstract = {The mitochondrial DNA COI barcode segment sequenced from American Anthocharis specimens across their distribution ranges partitions them into four well-separated species groups and reveals different levels of differentiation within these groups. The lanceolata group experienced the deepest divergence. About 2.7% barcode difference separates the two species: A. lanceolata Lucas, 1852 including A. lanceolata australis (F. Grinnell, 1908), from A. desertolimbus J. Emmel, T. Emmel & Mattoon, 1998. The sara group consists of three species distinctly defined by more than 2% sequence divergence: A. sara Lucas, 1852, A. julia W. H. Edwards, 1872, and A. thoosa (Scudder, 1878). Our treatment is fully consistent with morphological evidence largely based on the characters of fifth instar larvae and pupal cone curvature (Stout, 2005, 2018). In barcodes, it is not possible to see evidence of introgression or hybridization between the three species, and identification by morphology of immature stages always agrees with DNA barcode identification. Interestingly, A. thoosa exhibited the largest intraspecific divergence in DNA barcodes, and several of its metapopulations are identifiable by haplotypes. The cethura group is characterized by the smallest divergence and is best considered as a single species variable in expression of yellow coloration: A cethura C. Felder & R. Felder, 1865. Notably, the most sexually dimorphic subspecies A. cethura morrisoni W. H. Edwards, 1881 is the most distinct by the barcodes. Finally, the midea group barcodes do not always separate A. midea (Hübner, [1809]) and A. limonea (A. Butler, 1871) and we observe gradual accumulation of differences from north (northeastern USA) to south (Hidalgo, Mexico). This barcode gradient suggests a recent origin of the two midea group species and provides another example of vicariant sister species well defined by morphology, ecology and geography, but not necessarily by DNA barcodes.}, } @article {pmid37042115, year = {2023}, author = {Metcalfe, NB and Bellman, J and Bize, P and Blier, PU and Crespel, A and Dawson, NJ and Dunn, RE and Halsey, LG and Hood, WR and Hopkins, M and Killen, SS and McLennan, D and Nadler, LE and Nati, JJH and Noakes, MJ and Norin, T and Ozanne, SE and Peaker, M and Pettersen, AK and Przybylska-Piech, A and Rathery, A and Récapet, C and Rodríguez, E and Salin, K and Stier, A and Thoral, E and Westerterp, KR and Westerterp-Plantenga, MS and Wojciechowski, MS and Monaghan, P}, title = {Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {}, number = {}, pages = {e2300026}, doi = {10.1002/bies.202300026}, pmid = {37042115}, issn = {1521-1878}, abstract = {Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.}, } @article {pmid37029959, year = {2023}, author = {Galindo, LJ and Prokina, K and Torruella, G and Moreira, D and López-García, P}, title = {Maturases and Group II Introns in the Mitochondrial Genomes of the Deepest Jakobid Branch.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evad058}, pmid = {37029959}, issn = {1759-6653}, abstract = {Ophirinina is a recently described suborder of jakobid protists (Excavata) with only one described species to date, Ophirina amphinema. Despite the acquisition and analysis of massive transcriptomic and mitogenomic sequence data from O. amphinema, its phylogenetic position among excavates remained inconclusive, branching either as sister group to all Jakobida or to all Discoba. From a morphological perspective, it has several typical jakobid features but also unusual traits for this group, including the morphology of mitochondrial cristae (sac-shaped to flattened-curved cristae) and the presence of two flagellar vanes. In this study, we have isolated, morphologically characterized, and sequenced genome and transcriptome data of two new Ophirinina species: Ophirina chinija sp. nov. and Agogonia voluta gen. et sp. nov. Ophirina chinija differs from O. amphinema in having rounded cell ends, subapically emerging flagella and a posterior cell protrusion. The much more distantly related A. voluta has several unique ultrastructural characteristics, including sac-shaped mitochondrial cristae and a complex 'B' fibre. Phylogenomic analyses with a large conserved-marker dataset supported the monophyly of Ophirina and Agogonia within the Ophirinina and, more importantly, resolved the conflicting position of ophirinids as the sister clade to all other jakobids. The characterization of the mitochondrial genomes showed that Agogonia differs from all known gene-rich jakobid mitogenomes by the presence of two group II introns and their corresponding maturase protein genes. A phylogenetic analysis of the diversity of known maturases confirmed that the Agogonia proteins are highly divergent from each other and define distant families among the prokaryotic and eukaryotic maturases. This opens the intriguing possibility that, compared to other jakobids, Ophirinina may have retained additional mitochondrial elements that may help to understand the early diversification of eukaryotes and the evolution of mitochondria.}, } @article {pmid36326769, year = {2023}, author = {Kierepka, EM and Preckler-Quisquater, S and Reding, DM and Piaggio, AJ and Riley, SPD and Sacks, BN}, title = {Genomic analyses of gray fox lineages suggest ancient divergence and secondary contact in the southern Great Plains.}, journal = {The Journal of heredity}, volume = {114}, number = {2}, pages = {110-119}, doi = {10.1093/jhered/esac060}, pmid = {36326769}, issn = {1465-7333}, mesh = {Humans ; Animals ; *Foxes/genetics ; Phylogeny ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Genomics ; }, abstract = {The gray fox (Urocyon cinereoargenteus) lineage diverged from all other extant canids at their most basal node and is restricted to the Americas. Previous mitochondrial analysis from coastal populations identified deeply divergent (up to 1 Mya) eastern and western lineages that predate most intraspecific splits in carnivores. We conducted genotyping by sequencing and mitochondrial analysis on gray foxes sampled across North America to determine geographic concordance between nuclear and mitochondrial contact zones and divergence times. We also estimated the admixture within the contact zone between eastern and western gray foxes based on nuclear DNA. Both datasets confirmed that eastern and western lineages met in the southern Great Plains (i.e. Texas and Oklahoma), where they maintained high differentiation. Admixture was generally low, with the majority of admixed individuals carrying <10% ancestry from the other lineage. Divergence times confirmed a mid-Pleistocene split, similar to the mitochondrial estimates. Taken together, findings suggest gray fox lineages represent an ancient divergence event, far older than most intraspecific divergences in North American carnivores. Low admixture may reflect a relatively recent time since secondary contact (e.g. post-Pleistocene) or, alternatively, ecological or reproductive barriers between lineages. Though further research is needed to disentangle these factors, our genomic investigation suggests species-level divergence exists between eastern and western gray fox lineages.}, } @article {pmid37023388, year = {2023}, author = {Danial, JSH and Jenner, A and Garcia-Saez, AJ and Cosentino, K}, title = {Real-Time Growth Kinetics Analysis of Macromolecular Assemblies in Cells with Single Molecule Resolution.}, journal = {The journal of physical chemistry. A}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jpca.3c00368}, pmid = {37023388}, issn = {1520-5215}, abstract = {Single molecule fluorescence microscopy has the unique advantage to provide real-time information on the spatiotemporal assembly of individual protein complexes in cellular membranes. This includes the assembly of proteins into oligomer species of numerous copy numbers. However, there is a need for improved tracing analysis of the real-time growth kinetics of these assemblies in cells with single molecule resolution. Here, we present an automated analysis software to accurately measure the real-time kinetics of assembly of individual high-order oligomer complexes. Our software comes with a simple Graphical User Interface (GUI), is available as a source code and an executable, and can analyze a full data set of several hundred to thousand molecules in less than 2 minutes. Importantly, this software is suitable for the analysis of intracellular protein oligomers, whose stoichiometry is usually more difficult to quantify due to variability in signal detection in the different areas of the cell. We validated our method with simulated ground-truth data and time-lapse images of diffraction-limited oligomeric assemblies of BAX and BAK proteins on mitochondria of cells undergoing apoptosis. Our approach provides the broad community of biologists with a fast, user-friendly tool to trace the compositional evolution of macromolecular assemblies, and potentially model their growth for a deeper understanding of the structural and biophysical mechanisms underlying their functions.}, } @article {pmid37021319, year = {2023}, author = {Grosser, MR and Sites, SK and Murata, MM and Lopez, Y and Chamusco, KC and Love Harriage, K and Grosser, JW and Graham, JH and Gmitter, FG and Chase, CD}, title = {Plant mitochondrial introns as genetic markers - conservation and variation.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1116851}, pmid = {37021319}, issn = {1664-462X}, abstract = {Plant genomes are comprised of nuclear, plastid and mitochondrial components characterized by different patterns of inheritance and evolution. Genetic markers from the three genomes provide complementary tools for investigations of inheritance, genetic relationships and phenotypic contributions. Plant mitochondrial genomes are challenging for universal marker development because they are highly variable in terms of size, gene order and intergenic sequences and highly conserved with respect to protein-coding sequences. PCR amplification of introns with primers that anneal to conserved, flanking exons is effective for the development of polymorphic nuclear genome markers. The potential for plant mitochondrial intron polymorphisms to distinguish between congeneric species or intraspecific varieties has not been systematically investigated and is possibly constrained by requirements for intron secondary structure and interactions with co-evolved organelle intron splicing factors. To explore the potential for broadly applicable plant mitochondrial intron markers, PCR primer sets based upon conserved sequences flanking 11 introns common to seven angiosperm species were tested across a range of plant orders. PCR-amplified introns were screened for indel polymorphisms among a group of cross-compatible Citrus species and relatives; two Raphanus sativus mitotypes; representatives of the two Phaseolus vulgaris gene pools; and congeneric pairs of Cynodon, Cenchrus, Solanum, and Vaccinium species. All introns were successfully amplified from each plant entry. Length polymorphisms distinguishable by gel electrophoresis were common among genera but infrequent within genera. Sequencing of three introns amplified from 16 entries identified additional short indel polymorphisms and nucleotide substitutions that separated Citrus, Cynodon, Cenchrus and Vaccinium congeners, but failed to distinguish Solanum congeners or representatives of the Phaseolus vulgaris major gene pools. The ability of primer sets to amplify a wider range of plant species' introns and the presence of intron polymorphisms that distinguish congeners was confirmed by in silico analysis. While mitochondrial intron variation is limited in comparison to nuclear introns, these exon-based primer sets provide robust tools for the amplification of mitochondrial introns across a wide range of plant species wherein useful polymorphisms can be identified.}, } @article {pmid37017198, year = {2023}, author = {Parida, M and Gouda, G and Chidambaranathan, P and Umakanta, N and Katara, JL and Sai, CB and Samantaray, S and Patra, BC and Mohapatra, T}, title = {Mitochondrial markers differentiate two distinct phylogenetic groups in indigenous rice landraces of northeast India: an evolutionary insight.}, journal = {Journal of genetics}, volume = {102}, number = {}, pages = {}, pmid = {37017198}, issn = {0973-7731}, mesh = {Phylogeny ; *Oryza/genetics ; India ; }, abstract = {The inheritance of the mitochondria genome and its diversity is unique for genetic and evolutionary studies relative to nuclear genomes. Northeast India and Himalayan regions are considered as one of the centres of indica rice origin. Also, rice diversity in northeast India is very distinct and highly suited for evolutionary studies. Although reports are available on the genetic diversity of indigenous northeast rice landraces, its relationship with the wild relatives is not yet properly explored and understood. In an attempt, mitochondrial markers were used to study the evolutionary relationship between the 68 landraces of northeast India and wild relatives (O. rufipogon and O. nivara) along with IR64 (indica) and Nipponbare (japonica) were taken as reference cultivars. Phylogenetically, the findings include two distinct clusters in the indigenous northeast India landraces representing indica and japonica groups. Further, the wild relatives and ~60% of northeast India landraces were identified to be closely related to the Nipponbare cluster. Besides, landraces of northeast India grouping with the indica group (IR64) are characterized by the absence of wild relatives. This indicates that there are two distinct evolutionary paths in the origin of northeast Indian rice landraces based on mitochondrial markers diversity and it is proposed that the inheritance of mitochondria, mitonuclear genome interactions, and bottleneck events could have genetically separated these two phylogenetically unique groups of northeast rice landraces.}, } @article {pmid36994538, year = {2023}, author = {Qiu, L and Dong, J and Li, X and Parey, SH and Tan, K and Orr, M and Majeed, A and Zhang, X and Luo, S and Zhou, X and Zhu, C and Ji, T and Niu, Q and Liu, S and Zhou, X}, title = {Defining honeybee subspecies in an evolutionary context warrants strategized conservation.}, journal = {Zoological research}, volume = {44}, number = {3}, pages = {483-493}, doi = {10.24272/j.issn.2095-8137.2022.414}, pmid = {36994538}, issn = {2095-8137}, mesh = {Bees/genetics ; Animals ; Phylogeny ; Phenotype ; *Mitochondria ; }, abstract = {Despite the urgent need for conservation consideration, strategic action plans for the preservation of the Asian honeybee, Apis cerana Fabricius, 1793, remain lacking. Both the convergent and divergent adaptations of this widespread insect have led to confusing phenotypical traits and inconsistent infraspecific taxonomy. Unclear subspecies boundaries pose a significant challenge to honeybee conservation efforts, as it is difficult to effectively prioritize conservation targets without a clear understanding of subspecies identities. Here, we investigated genome variations in 362 worker bees representing almost all populations of mainland A. cerana to understand how evolution has shaped its population structure. Whole-genome single nucleotide polymorphisms (SNPs) based on nuclear sequences revealed eight putative subspecies, with all seven peripheral subspecies exhibiting mutually exclusive monophyly and distinct genetic divergence from the widespread central subspecies. Our results demonstrated that most classic morphological traits, including body size, were related to the climatic variables of the local habitats and did not reflect the true evolutionary history of the organism. Thus, such morphological traits were not suitable for subspecific delineation. Conversely, wing vein characters showed relative independence to the environment and supported the subspecies boundaries inferred from nuclear genomes. Mitochondrial phylogeny further indicated that the present subspecies structure was a result of multiple waves of population divergence from a common ancestor. Based on our findings, we propose that criteria for subspecies delineation should be based on evolutionary independence, trait distinction, and geographic isolation. We formally defined and described eight subspecies of mainland A. cerana. Elucidation of the evolutionary history and subspecies boundaries enables a customized conservation strategy for both widespread and endemic honeybee conservation units, guiding colony introduction and breeding.}, } @article {pmid36695030, year = {2023}, author = {Röhricht, H and Przybyla-Toscano, J and Forner, J and Boussardon, C and Keech, O and Rouhier, N and Meyer, EH}, title = {Mitochondrial ferredoxin-like is essential for forming complex I-containing supercomplexes in Arabidopsis.}, journal = {Plant physiology}, volume = {191}, number = {4}, pages = {2170-2184}, pmid = {36695030}, issn = {1532-2548}, mesh = {*Ferredoxins/genetics/metabolism ; *Arabidopsis/genetics/metabolism ; Phylogeny ; Electron Transport Complex I/genetics/metabolism ; Mitochondria/metabolism ; }, abstract = {In eukaryotes, mitochondrial ATP is mainly produced by the oxidative phosphorylation (OXPHOS) system, which is composed of 5 multiprotein complexes (complexes I-V). Analyses of the OXPHOS system by native gel electrophoresis have revealed an organization of OXPHOS complexes into supercomplexes, but their roles and assembly pathways remain unclear. In this study, we characterized an atypical mitochondrial ferredoxin (mitochondrial ferredoxin-like, mFDX-like). This protein was previously found to be part of the bridge domain linking the matrix and membrane arms of the complex I. Phylogenetic analysis suggested that the Arabidopsis (Arabidopsis thaliana) mFDX-like evolved from classical mitochondrial ferredoxins (mFDXs) but lost one of the cysteines required for the coordination of the iron-sulfur (Fe-S) cluster, supposedly essential for the electron transfer function of FDXs. Accordingly, our biochemical study showed that AtmFDX-like does not bind an Fe-S cluster and is therefore unlikely to be involved in electron transfer reactions. To study the function of mFDX-like, we created deletion lines in Arabidopsis using a CRISPR/Cas9-based strategy. These lines did not show any abnormal phenotype under standard growth conditions. However, the characterization of the OXPHOS system demonstrated that mFDX-like is important for the assembly of complex I and essential for the formation of complex I-containing supercomplexes. We propose that mFDX-like and the bridge domain are required for the correct conformation of the membrane arm of complex I that is essential for the association of complex I with complex III2 to form supercomplexes.}, } @article {pmid36921565, year = {2023}, author = {Huang, L and Zhang, L and Shi, S and Zhou, X and Yuan, H and Song, X and Hu, Y and Pang, W and Yang, G and Gao, L and Chu, G}, title = {Mitochondrial function and E2 synthesis are impaired following alteration of CLOCK gene expression in porcine ovarian granulosa cells.}, journal = {Theriogenology}, volume = {202}, number = {}, pages = {51-60}, doi = {10.1016/j.theriogenology.2023.03.004}, pmid = {36921565}, issn = {1879-3231}, mesh = {Female ; Swine ; Animals ; *Gene Expression Regulation ; Phylogeny ; *Granulosa Cells/physiology ; Estradiol/metabolism ; Mitochondria/metabolism ; Gene Expression ; Mammals ; }, abstract = {Circadian locomotor output cycles kaput (CLOCK) is a critical component of the mammalian circadian clock system and regulates ovarian physiology. However, the functions and mechanisms of CLOCK in porcine granulosa cells (GCs) are poorly understood. The present study focused on CLOCK's effects on estradiol synthesis. Similarity analysis showed that CLOCK is highly conserved between pigs and other species. The phylogenetic tree analysis indicated that porcine CLOCK was most closely related to that in Arabian camels. CLOCK significantly reduced E2 synthesis in GCs. CLOCK reduced the expression of steroidogenesis-related genes at the mRNA and protein levels, including CYP19A1, CYP11A1, and StAR. CYP17A1 levels were significantly downregulated. We demonstrated that CLOCK dramatically decreased ATP content, mitochondrial copy number, and mitochondrial membrane potential (MMP) and increased reactive oxygen species levels in GCs. We observed that mitochondria were severely damaged with fuzzy and fractured cristae and swollen matrix. These findings suggest that mitochondrial function and E2 synthesis are impaired following the alteration of CLOCK gene expression in porcine ovarian GCs.}, } @article {pmid36993903, year = {2023}, author = {Dalle Carbonare, L and Jiménez, JC and Lichtenauer, S and van Veen, H}, title = {Plant responses to limited aeration: Advances and future challenges.}, journal = {Plant direct}, volume = {7}, number = {3}, pages = {e488}, pmid = {36993903}, issn = {2475-4455}, abstract = {Limited aeration that is caused by tissue geometry, diffusion barriers, high elevation, or a flooding event poses major challenges to plants and is often, but not exclusively, associated with low oxygen. These processes span a broad interest in the research community ranging from whole plant and crop responses, post-harvest physiology, plant morphology and anatomy, fermentative metabolism, plant developmental processes, oxygen sensing by ERF-VIIs, gene expression profiles, the gaseous hormone ethylene, and O2 dynamics at cellular resolution. The International Society for Plant Anaerobiosis (ISPA) gathers researchers from all over the world contributing to understand the causes, responses, and consequences of limited aeration in plants. During the 14th ISPA meeting, major research progress was related to the evolution of O2 sensing mechanisms and the intricate network that balances low O2 signaling. Here, the work moved beyond flooding stress and emphasized novel underexplored roles of low O2 and limited aeration in altitude adaptation, fruit development and storage, and the vegetative development of growth apices. Regarding tolerance towards flooding, the meeting stressed the relevance and regulation of developmental plasticity, aerenchyma, and barrier formation to improve internal aeration. Additional newly explored flood tolerance traits concerned resource balance, senescence, and the exploration of natural genetic variation for novel tolerance loci. In this report, we summarize and synthesize the major progress and future challenges for low O2 and aeration research presented at the conference.}, } @article {pmid36949187, year = {2023}, author = {Mühleip, A and Flygaard, RK and Baradaran, R and Haapanen, O and Gruhl, T and Tobiasson, V and Maréchal, A and Sharma, V and Amunts, A}, title = {Structural basis of mitochondrial membrane bending by the I-II-III2-IV2 supercomplex.}, journal = {Nature}, volume = {615}, number = {7954}, pages = {934-938}, pmid = {36949187}, issn = {1476-4687}, mesh = {*Mitochondrial Membranes/metabolism ; Cryoelectron Microscopy/methods ; *Mitochondria/metabolism ; Electron Transport ; Electron Transport Complex IV/chemistry/metabolism ; Electron Transport Complex III/metabolism ; }, abstract = {Mitochondrial energy conversion requires an intricate architecture of the inner mitochondrial membrane[1]. Here we show that a supercomplex containing all four respiratory chain components contributes to membrane curvature induction in ciliates. We report cryo-electron microscopy and cryo-tomography structures of the supercomplex that comprises 150 different proteins and 311 bound lipids, forming a stable 5.8-MDa assembly. Owing to subunit acquisition and extension, complex I associates with a complex IV dimer, generating a wedge-shaped gap that serves as a binding site for complex II. Together with a tilted complex III dimer association, it results in a curved membrane region. Using molecular dynamics simulations, we demonstrate that the divergent supercomplex actively contributes to the membrane curvature induction and tubulation of cristae. Our findings highlight how the evolution of protein subunits of respiratory complexes has led to the I-II-III2-IV2 supercomplex that contributes to the shaping of the bioenergetic membrane, thereby enabling its functional specialization.}, } @article {pmid36981035, year = {2023}, author = {Kundu, S and Kamalakannan, M and Mukherjee, T and Banerjee, D and Kim, HW}, title = {Genetic Characterization and Insular Habitat Enveloping of Endangered Leaf-Nosed Bat, Hipposideros nicobarulae (Mammalia: Chiroptera) in India: Phylogenetic Inference and Conservation Implication.}, journal = {Genes}, volume = {14}, number = {3}, pages = {}, pmid = {36981035}, issn = {2073-4425}, mesh = {Animals ; *Chiroptera/genetics ; Phylogeny ; Bayes Theorem ; Mammals ; Mitochondria ; }, abstract = {The Nicobar leaf-nosed Bat (Hipposideros nicobarulae) was described in the early 20th century; however, its systematic classification has been debated for over 100 years. This endangered and endemic species has achieved species status through morphological data in the last 10 years. However, the genetic information and phylogenetic relationships of H. nicobarulae remain neglected. The generated mitochondrial cytochrome b gene (mtCytb) sequences (438 bp) of H. nicobarulae contains 53.42-53.65% AT composition and 1.82% variable sites. The studied species, H. nicobarulae maintains an 8.1% to 22.6% genetic distance from other Hipposideros species. The genetic divergence estimated in this study is congruent with the concept of gene speciation in bats. The Bayesian and Maximum-Likelihood phylogenies clearly discriminated all Hipposideros species and showed a sister relationship between H. nicobarulae and H. cf. antricola. Current mtCytb-based investigations of H. nicobarulae have confirmed the species status at the molecular level. Further, the MaxEnt-based species distribution modelling illustrates the most suitable habitat of H. nicobarulae (294 km[2]), of which the majority (171 km[2]) is located on Great Nicobar Island. The present study suggests rigorous sampling across the range, taxonomic coverage, the generation of multiple molecular markers (mitochondrial and nuclear), as well as more ecological information, which will help in understanding population genetic structure, habitat suitability, and the implementation of appropriate conservation action plans for H. nicobarulae and other Hipposideros species.}, } @article {pmid36980901, year = {2023}, author = {Hammar, F and Miller, DL}, title = {Genetic Diversity in the mtDNA of Physarum polycephalum.}, journal = {Genes}, volume = {14}, number = {3}, pages = {}, pmid = {36980901}, issn = {2073-4425}, mesh = {*Physarum polycephalum/genetics ; DNA, Mitochondrial/genetics ; Base Sequence ; Mitochondria/genetics ; Genetic Variation/genetics ; }, abstract = {The mtDNA of the myxomycete Physarum polycephalum can contain as many as 81 genes. These genes can be grouped in three different categories. The first category includes 46 genes that are classically found on the mtDNA of many organisms. However, 43 of these genes are cryptogenes that require a unique type of RNA editing (MICOTREM). A second category of gene is putative protein-coding genes represented by 26 significant open reading frames. However, these genes do not appear to be transcribed during the growth of the plasmodium and are currently unassigned since they do not have any apparent similarity to other classical mitochondrial protein-coding genes. The third category of gene is found in the mtDNA of some strains of P. polycephalum. These genes derive from a linear mitochondrial plasmid with nine significant, but unassigned, open reading frames which can integrate into the mitochondrial DNA by recombination. Here, we review the mechanism and evolution of the RNA editing necessary for cryptogene expression, discuss possible origins for the 26 unassigned open reading frames based on tentative identification of their protein product, and discuss the implications to mtDNA structure and replication of the integration of the linear mitochondrial plasmid.}, } @article {pmid36977381, year = {2023}, author = {Michels, PAM and Ginger, ML}, title = {Evolution: 'Millefoglie' origin of mitochondrial cristae.}, journal = {Current biology : CB}, volume = {33}, number = {6}, pages = {R219-R221}, doi = {10.1016/j.cub.2023.02.037}, pmid = {36977381}, issn = {1879-0445}, mesh = {*Mitochondria/genetics/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; Mitochondrial Membranes/metabolism ; }, abstract = {Striated intracytoplasmic membranes in alphaproteobacteria are often reminiscent of millefoglie pastries. A new study reveals a protein complex homologous to that responsible for mitochondrial cristae formation drives intracytoplasmic membrane formation, thereby establishing bacterial ancestry for the biogenesis of mitochondrial cristae.}, } @article {pmid36971557, year = {2023}, author = {Shaliutina-Loginova, A and Francetic, O and Doležal, P}, title = {Bacterial Type II Secretion System and Its Mitochondrial Counterpart.}, journal = {mBio}, volume = {}, number = {}, pages = {e0314522}, doi = {10.1128/mbio.03145-22}, pmid = {36971557}, issn = {2150-7511}, abstract = {Over the billions of years that bacteria have been around, they have evolved several sophisticated protein secretion nanomachines to deliver toxins, hydrolytic enzymes, and effector proteins into their environments. Of these, the type II secretion system (T2SS) is used by Gram-negative bacteria to export a wide range of folded proteins from the periplasm across the outer membrane. Recent findings have demonstrated that components of the T2SS are localized in mitochondria of some eukaryotic lineages, and their behavior is consistent with the presence of a mitochondrial T2SS-derived system (miT2SS). This review focuses on recent advances in the field and discusses open questions concerning the function and evolution of miT2SSs.}, } @article {pmid36921606, year = {2023}, author = {Muñoz-Gómez, SA and Cadena, LR and Gardiner, AT and Leger, MM and Sheikh, S and Connell, LB and Bilý, T and Kopejtka, K and Beatty, JT and Koblížek, M and Roger, AJ and Slamovits, CH and Lukeš, J and Hashimi, H}, title = {Intracytoplasmic-membrane development in alphaproteobacteria involves the homolog of the mitochondrial crista-developing protein Mic60.}, journal = {Current biology : CB}, volume = {33}, number = {6}, pages = {1099-1111.e6}, doi = {10.1016/j.cub.2023.02.059}, pmid = {36921606}, issn = {1879-0445}, mesh = {*Mitochondrial Proteins/metabolism ; *Alphaproteobacteria/genetics/metabolism ; Mitochondrial Membranes/metabolism ; Mitochondria/metabolism ; Biological Evolution ; }, abstract = {Mitochondrial cristae expand the surface area of respiratory membranes and ultimately allow for the evolutionary scaling of respiration with cell volume across eukaryotes. The discovery of Mic60 homologs among alphaproteobacteria, the closest extant relatives of mitochondria, suggested that cristae might have evolved from bacterial intracytoplasmic membranes (ICMs). Here, we investigated the predicted structure and function of alphaproteobacterial Mic60, and a protein encoded by an adjacent gene Orf52, in two distantly related purple alphaproteobacteria, Rhodobacter sphaeroides and Rhodopseudomonas palustris. In addition, we assessed the potential physical interactors of Mic60 and Orf52 in R. sphaeroides. We show that the three α helices of mitochondrial Mic60's mitofilin domain, as well as its adjacent membrane-binding amphipathic helix, are present in alphaproteobacterial Mic60. The disruption of Mic60 and Orf52 caused photoheterotrophic growth defects, which are most severe under low light conditions, and both their disruption and overexpression led to enlarged ICMs in both studied alphaproteobacteria. We also found that alphaproteobacterial Mic60 physically interacts with BamA, the homolog of Sam50, one of the main physical interactors of eukaryotic Mic60. This interaction, responsible for making contact sites at mitochondrial envelopes, has been conserved in modern alphaproteobacteria despite more than a billion years of evolutionary divergence. Our results suggest a role for Mic60 in photosynthetic ICM development and contact site formation at alphaproteobacterial envelopes. Overall, we provide support for the hypothesis that mitochondrial cristae evolved from alphaproteobacterial ICMs and have therefore improved our understanding of the nature of the mitochondrial ancestor.}, } @article {pmid36964263, year = {2023}, author = {Jablonski, D and Ribeiro-Júnior, MA and Simonov, E and Šoltys, K and Meiri, S}, title = {A new, rare, small-ranged, and endangered mountain snake of the genus Elaphe from the Southern Levant.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {4839}, pmid = {36964263}, issn = {2045-2322}, mesh = {Animals ; Phylogeny ; *Colubridae ; Mitochondria/genetics ; Lebanon ; Syria ; DNA, Mitochondrial/genetics ; }, abstract = {The genus Elaphe Fitzinger, 1833 includes 17 species of charismatic, large-sized, non-venomous, Eurasian snakes. In the Western Palearctic, the genus is represented by three species from the Elaphe quatuorlineata group ranging from the Apennine peninsula to Central Asia. The southernmost population of this group is distributed in the mountains of the Southern Levant, with more than 400 km gap to other Elaphe populations. This population has been known to science for only 50 years and is virtually unstudied due to its extreme rarity. We studied these snakes' morphological and genetic variation from the three countries where they are known to occur, i.e., Israel (Hermon, the Israeli-controlled Golan Heights), Lebanon, and Syria. We used nine mitochondrial and nuclear genes, complete mitogenome sequences, and a comprehensive morphological examination including published data, our own field observations, and museum specimens, to study its relationship to other species in the group. The three currently recognized species of the group (E. quatuorlineata, E. sauromates, E. urartica), and the Levant population, form four deeply divergent, strongly supported clades. Three of these clades correspond to the abovementioned species while the Southern Levant clade, which is genetically and morphologically distinct from all named congeners, is described here as a new species, Elaphe druzei sp. nov. The basal divergence of this group is estimated to be the Late Miocene with subsequent radiation from 5.1 to 3.9 Mya. The revealed biogeography of the E. quatuorlineata group supports the importance of the Levant as a major center of endemism and diversity of biota in Eurasia. The new species is large-sized and is one of the rarest snakes in the Western Palearctic. Because of its small mountain distribution range, in an area affected by land use and climate change, the new Elaphe urgently needs strict protection. Despite political issues, we hope this will be based on the cooperation of all countries where the new species occurs.}, } @article {pmid36889655, year = {2023}, author = {Zhu, X and Liu, T and He, A and Zhang, L and Li, J and Li, T and Miao, X and You, M and You, S}, title = {Diversity of Wolbachia infection and its influence on mitochondrial DNA variation in the diamondback moth, Plutella xylostella.}, journal = {Molecular phylogenetics and evolution}, volume = {182}, number = {}, pages = {107751}, doi = {10.1016/j.ympev.2023.107751}, pmid = {36889655}, issn = {1095-9513}, mesh = {Animals ; *Moths/genetics ; *Wolbachia/genetics ; Phylogeny ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {Plutella xylostella is a pest that severely damages cruciferous vegetables worldwide and has been shown to be infected with the maternally inherited bacteria Wolbachia, with the main infected strain was plutWB1. In this study, we performed a large-scale global sampling of P. xylostella and amplified 3 mtDNA genes of P. xylostella and 6 Wolbachia genes to analyze the infection status, diversity of Wolbachia in P. xylostella, and its effect on mtDNA variation in P. xylostella. This study provides a conservative estimate of Wolbachia infection rates in P. xylostella, which was found to be 7% (104/1440). The ST 108 (plutWB1) was shared among butterfly species and the moth species P. xylostella, revealing that Wolbachia strain plutWB1 acquisition in P. xylostella may be through horizontal transmission. The Parafit analyses indicated a significant association between Wolbachia and Wolbachia-infected P. xylostella individuals, and individuals infected with plutWB1 tended to cluster in the basal positions of the phylogenetic tree based on the mtDNA data. Additionally, Wolbachia infections were associated with increased mtDNA polymorphism in the infected P. xylostella population. These data suggest that Wolbachia endosymbionts may have a potential effect on mtDNA variation of P. xylostella.}, } @article {pmid36773750, year = {2023}, author = {Taite, M and Fernández-Álvarez, FÁ and Braid, HE and Bush, SL and Bolstad, K and Drewery, J and Mills, S and Strugnell, JM and Vecchione, M and Villanueva, R and Voight, JR and Allcock, AL}, title = {Genome skimming elucidates the evolutionary history of Octopoda.}, journal = {Molecular phylogenetics and evolution}, volume = {182}, number = {}, pages = {107729}, doi = {10.1016/j.ympev.2023.107729}, pmid = {36773750}, issn = {1095-9513}, mesh = {Animals ; *Octopodiformes/genetics ; Phylogeny ; Bayes Theorem ; Mitochondria/genetics ; *Genome, Mitochondrial ; RNA, Transfer ; }, abstract = {Phylogenies for Octopoda have, until now, been based on morphological characters or a few genes. Here we provide the complete mitogenomes and the nuclear 18S and 28S ribosomal genes of twenty Octopoda specimens, comprising 18 species of Cirrata and Incirrata, representing 13 genera and all five putative families of Cirrata (Cirroctopodidae, Cirroteuthidae, Grimpoteuthidae, Opisthoteuthidae and Stauroteuthidae) and six families of Incirrata (Amphitretidae, Argonautidae, Bathypolypodidae, Eledonidae, Enteroctopodidae, and Megaleledonidae) which were assembled using genome skimming. Phylogenetic trees were built using Maximum Likelihood and Bayesian Inference with several alignment matrices. All mitochondrial genomes had the 'typical' genome composition and gene order previously reported for octopodiforms, except Bathypolypus ergasticus, which appears to lack ND5, two tRNA genes that flank ND5 and two other tRNA genes. Argonautoidea was revealed as sister to Octopodidae by the mitochondrial protein-coding gene dataset, however, it was recovered as sister to all other incirrate octopods with strong support in an analysis using nuclear rRNA genes. Within Cirrata, our study supports two existing classifications suggesting neither is likely in conflict with the true evolutionary history of the suborder. Genome skimming is useful in the analysis of phylogenetic relationships within Octopoda; inclusion of both mitochondrial and nuclear data may be key.}, } @article {pmid36966978, year = {2023}, author = {Edera, AA and Howell, KA and Nevill, PG and Small, I and Virginia Sanchez-Puerta, M}, title = {Evolution of cox2 introns in angiosperm mitochondria and efficient splicing of an elongated cox2i691 intron.}, journal = {Gene}, volume = {}, number = {}, pages = {147393}, doi = {10.1016/j.gene.2023.147393}, pmid = {36966978}, issn = {1879-0038}, abstract = {In angiosperms, the mitochondrial cox2 gene harbors up to two introns, commonly referred to as cox2i373 and cox2i691. We studied the cox2 from 222 fully-sequenced mitogenomes from 30 angiosperm orders and analyzed the evolution of its introns. Unlike cox2i373, cox2i691 shows a distribution among plants that is shaped by frequent intron loss events driven by localized retroprocessing. In addition, cox2i691 exhibits sporadic elongations, presumably in domain IV of the intron. Such elongations are poorly related to repeat content and two of them showed the presence of LINE transposons, suggesting that increasing intron size is very likely due to nuclear intracelular DNA transfer followed by incorporation into the mitochondrial DNA. Surprisingly, we found that cox2i691 is erroneously annotated as absent in 30 mitogenomes deposited in public databases. Although each of the cox2 introns is ∼1.5 kb in length, a cox2i691 of 4.2 kb has been reported in Acacia ligulata (Fabaceae). It is still unclear whether its unusual length is due to a trans-splicing arrangement or the loss of functionality of the interrupted cox2. Through analyzing short-read RNA sequencing of Acacia with a multi-step computational strategy, we found that the Acacia cox2 is functional and its long intron is spliced in cis in a very efficient manner despite its length.}, } @article {pmid36965057, year = {2023}, author = {Speijer, D}, title = {How mitochondria showcase evolutionary mechanisms and the importance of oxygen.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {}, number = {}, pages = {e2300013}, doi = {10.1002/bies.202300013}, pmid = {36965057}, issn = {1521-1878}, abstract = {Darwinian evolution can be simply stated: natural selection of inherited variations increasing differential reproduction. However, formulated thus, links with biochemistry, cell biology, ecology, and population dynamics remain unclear. To understand interactive contributions of chance and selection, higher levels of biological organization (e.g., endosymbiosis), complexities of competing selection forces, and emerging biological novelties (such as eukaryotes or meiotic sex), we must analyze actual examples. Focusing on mitochondria, I will illuminate how biology makes sense of life's evolution, and the concepts involved. First, looking at the bacterium - mitochondrion transition: merging with an archaeon, it lost its independence, but played a decisive role in eukaryogenesis, as an extremely efficient aerobic ATP generator and internal ROS source. Second, surveying later mitochondrion adaptations and diversifications illustrates concepts such as constructive neutral evolution, dynamic interactions between endosymbionts and hosts, the contingency of life histories, and metabolic reprogramming. Without oxygen, mitochondria disappear; with (intermittent) oxygen diversification occurs in highly complex ways, especially upon (temporary) phototrophic substrate supply. These expositions show the Darwinian model to be a highly fruitful paradigm.}, } @article {pmid36951086, year = {2023}, author = {Sloan, DB and DeTar, RA and Warren, JM}, title = {Aminoacyl-tRNA synthetase evolution within the dynamic tripartite translation system of plant cells.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evad050}, pmid = {36951086}, issn = {1759-6653}, abstract = {Eukaryotes maintain separate protein translation systems for nuclear and organellar genes, including distinct sets of tRNAs and aminoacyl-tRNA synthetases (aaRSs). In animals, mitochondrial-targeted aaRSs are expressed at lower levels and are less conserved in sequence than cytosolic aaRSs involved in translation of nuclear mRNAs, likely reflecting lower translational demands in mitochondria. In plants, translation is further complicated by the presence of plastids, which share most aaRSs with mitochondria. In addition, plant mitochondrial tRNA pools have a dynamic history of gene loss and functional replacement by tRNAs from other compartments. To investigate the consequences of these distinctive features of translation in plants, we analyzed sequence evolution in angiosperm aaRSs. In contrast to previously studied eukaryotic systems, we found that plant organellar and cytosolic aaRSs exhibit only a small difference in expression levels, and organellar aaRSs are slightly more conserved than cytosolic aaRSs. We hypothesize that these patterns result from high translational demands associated with photosynthesis in mature chloroplasts. We also investigated aaRS evolution in Sileneae, an angiosperm lineage with extensive mitochondrial tRNA replacement and aaRS retargeting. We predicted positive selection for changes in aaRS sequence resulting from these recent changes in subcellular localization and tRNA substrates but found little evidence for accelerated sequence divergence. Overall, the complex tripartite translation system in plant cells appears to have imposed more constraints on the long-term evolutionary rates of organellar aaRSs compared to other eukaryotic lineages, and plant aaRS protein sequences appear largely robust to more recent perturbations in subcellular localization and tRNA interactions.}, } @article {pmid36948470, year = {2023}, author = {Cayuela, H and Gaillard, JM and Vieira, C and Ronget, V and Gippet, JMW and Garcia, TC and Marais, GAB and Lemaître, JF}, title = {Sex differences in adult lifespan and aging rate across mammals: a test of the 'Mother Curse hypothesis'.}, journal = {Mechanisms of ageing and development}, volume = {}, number = {}, pages = {111799}, doi = {10.1016/j.mad.2023.111799}, pmid = {36948470}, issn = {1872-6216}, abstract = {In many animal species, including humans, males have shorter lifespan and show faster survival aging than females. This differential increase in mortality between sexes could result from the accumulation of deleterious mutations in the mitochondrial genome of males due to the maternal mode of mtDNA inheritance. To date, empirical evidence supporting the existence of this mechanism - called the Mother Curse hypothesis - remains largely limited to a few study cases in humans and Drosophila. In this study, we tested whether the Mother Curse hypothesis accounts for sex differences in lifespan and aging rate across 128 populations of mammals (60 and 68 populations studied in wild and captive conditions, respectively) encompassing 104 species. We found that adult lifespan decreases with increasing mtDNA neutral substitution rate in both sexes in a similar way in the wild - but not in captivity. Moreover, the aging rate marginally increased with neutral substitution rate in males and females in the wild. Overall, these results indicate that the Mother Curse hypothesis is not supported across mammals. We further discuss the implication of these findings for our understanding of the evolution of sex differences in mortality and aging.}, } @article {pmid36948134, year = {2023}, author = {Celik, A and Orfany, A and Dearling, J and Del Nido, PJ and McCully, JD and Bakar-Ates, F}, title = {Mitochondrial transplantation: Effects on chemotherapy in prostate and ovarian cancer cells in vitro and in vivo.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {161}, number = {}, pages = {114524}, doi = {10.1016/j.biopha.2023.114524}, pmid = {36948134}, issn = {1950-6007}, abstract = {Prostate and ovarian cancers affect the male and female reproductive organs and are among the most common cancers in developing countries. Previous studies have demonstrated that cancer cells have a high rate of aerobic glycolysis that is present in nearly all invasive human cancers and persists even under normoxic conditions. Aerobic glycolysis has been correlated with chemotherapeutic resistance and tumor aggressiveness. These data suggest that mitochondrial dysfunction may confer a significant proliferative advantage during the somatic evolution of cancer. In this study we investigated the effect of direct mitochondria transplantation on cancer cell proliferation and chemotherapeutic sensitivity in prostate and ovarian cancer models, both in vitro and in vivo. Our results show that the transplantation of viable, respiration competent mitochondria has no effect on cancer cell proliferation but significantly decreases migration and alters cell cycle checkpoints. Our results further demonstrate that mitochondrial transplantation significantly increases chemotherapeutic sensitivity, providing similar apoptotic levels with low-dose chemotherapy as that achieved with high-dose chemotherapy. These results suggest that mitochondria transplantation provides a novel approach for early prostate and ovarian cancer therapy, significantly increasing chemotherapeutic sensitivity in in vitro and in vivo murine models.}, } @article {pmid36944988, year = {2023}, author = {Yu, X and Wei, P and Chen, Z and Li, X and Zhang, W and Yang, Y and Liu, C and Zhao, S and Li, X and Liu, X}, title = {Comparative analysis of the organelle genomes of three Rhodiola species provide insights into their structural dynamics and sequence divergences.}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {156}, pmid = {36944988}, issn = {1471-2229}, abstract = {BACKGROUND: Plant organelle genomes are a valuable resource for evolutionary biology research, yet their genome architectures, evolutionary patterns and environmental adaptations are poorly understood in many lineages. Rhodiola species is a type of flora mainly distributed in highland habitats, with high medicinal value. Here, we assembled the organelle genomes of three Rhodiola species (R. wallichiana, R. crenulata and R. sacra) collected from the Qinghai-Tibet plateau (QTP), and compared their genome structure, gene content, structural rearrangements, sequence transfer and sequence evolution rates.

RESULTS: The results demonstrated the contrasting evolutionary pattern between plastomes and mitogenomes in three Rhodiola species, with the former possessing more conserved genome structure but faster evolutionary rates of sequence, while the latter exhibiting structural diversity but slower rates of sequence evolution. Some lineage-specific features were observed in Rhodiola mitogenomes, including chromosome fission, gene loss and structural rearrangement. Repeat element analysis shows that the repeats occurring between the two chromosomes may mediate the formation of multichromosomal structure in the mitogenomes of Rhodiola, and this multichromosomal structure may have recently formed. The identification of homologous sequences between plastomes and mitogenomes reveals several unidirectional protein-coding gene transfer events from chloroplasts to mitochondria. Moreover, we found that their organelle genomes contained multiple fragments of nuclear transposable elements (TEs) and exhibited different preferences for TEs insertion type. Genome-wide scans of positive selection identified one gene matR from the mitogenome. Since the matR is crucial for plant growth and development, as well as for respiration and stress responses, our findings suggest that matR may participate in the adaptive response of Rhodiola species to environmental stress of QTP.

CONCLUSION: The study analyzed the organelle genomes of three Rhodiola species and demonstrated the contrasting evolutionary pattern between plastomes and mitogenomes. Signals of positive selection were detected in the matR gene of Rhodiola mitogenomes, suggesting the potential role of this gene in Rhodiola adaptation to QTP. Together, the study is expected to enrich the genomic resources and provide valuable insights into the structural dynamics and sequence divergences of Rhodiola species.}, } @article {pmid36939357, year = {2023}, author = {Macher, JN and Coots, NL and Poh, YP and Girard, EB and Langerak, A and Muñoz-Gómez, SA and Sinha, SD and Jirsová, D and Vos, R and Wissels, R and Gile, GH and Renema, W and Wideman, JG}, title = {Single-Cell Genomics Reveals the Divergent Mitochondrial Genomes of Retaria (Foraminifera and Radiolaria).}, journal = {mBio}, volume = {}, number = {}, pages = {e0030223}, doi = {10.1128/mbio.00302-23}, pmid = {36939357}, issn = {2150-7511}, abstract = {Mitochondria originated from an ancient bacterial endosymbiont that underwent reductive evolution by gene loss and endosymbiont gene transfer to the nuclear genome. The diversity of mitochondrial genomes published to date has revealed that gene loss and transfer processes are ongoing in many lineages. Most well-studied eukaryotic lineages are represented in mitochondrial genome databases, except for the superphylum Retaria-the lineage comprising Foraminifera and Radiolaria. Using single-cell approaches, we determined two complete mitochondrial genomes of Foraminifera and two nearly complete mitochondrial genomes of radiolarians. We report the complete coding content of an additional 14 foram species. We show that foraminiferan and radiolarian mitochondrial genomes contain a nearly fully overlapping but reduced mitochondrial gene complement compared to other sequenced rhizarians. In contrast to animals and fungi, many protists encode a diverse set of proteins on their mitochondrial genomes, including several ribosomal genes; however, some aerobic eukaryotic lineages (euglenids, myzozoans, and chlamydomonas-like algae) have reduced mitochondrial gene content and lack all ribosomal genes. Similar to these reduced outliers, we show that retarian mitochondrial genomes lack ribosomal protein and tRNA genes, contain truncated and divergent small and large rRNA genes, and contain only 14 or 15 protein-coding genes, including nad1, -3, -4, -4L, -5, and -7, cob, cox1, -2, and -3, and atp1, -6, and -9, with forams and radiolarians additionally carrying nad2 and nad6, respectively. In radiolarian mitogenomes, a noncanonical genetic code was identified in which all three stop codons encode amino acids. Collectively, these results add to our understanding of mitochondrial genome evolution and fill in one of the last major gaps in mitochondrial sequence databases. IMPORTANCE We present the reduced mitochondrial genomes of Retaria, the rhizarian lineage comprising the phyla Foraminifera and Radiolaria. By applying single-cell genomic approaches, we found that foraminiferan and radiolarian mitochondrial genomes contain an overlapping but reduced mitochondrial gene complement compared to other sequenced rhizarians. An alternative genetic code was identified in radiolarian mitogenomes in which all three stop codons encode amino acids. Collectively, these results shed light on the divergent nature of the mitochondrial genomes from an ecologically important group, warranting further questions into the biological underpinnings of gene content variability and genetic code variation between mitochondrial genomes.}, } @article {pmid36916992, year = {2023}, author = {Monné, M and Cianciulli, A and Panaro, MA and Calvello, R and De Grassi, A and Palmieri, L and Mitolo, V and Palmieri, F}, title = {New Insights into the Evolution and Gene Structure of the Mitochondrial Carrier Family Unveiled by Analyzing the Frequent and Conserved Intron Positions.}, journal = {Molecular biology and evolution}, volume = {40}, number = {3}, pages = {}, pmid = {36916992}, issn = {1537-1719}, mesh = {Humans ; Introns ; Phylogeny ; *Mitochondria/genetics/metabolism ; *Membrane Transport Proteins/genetics ; Eukaryota/genetics ; Evolution, Molecular ; Conserved Sequence ; }, abstract = {Mitochondrial carriers (MCs) belong to a eukaryotic protein family of transporters that in higher organisms is called the solute carrier family 25 (SLC25). All MCs have characteristic triplicated sequence repeats forming a 3-fold symmetrical structure of a six-transmembrane α-helix bundle with a centrally located substrate-binding site. Biochemical characterization has shown that MCs altogether transport a wide variety of substrates but can be divided into subfamilies, each transporting a few specific substrates. We have investigated the intron positions in the human MC genes and their orthologs of highly diversified organisms. The results demonstrate that several intron positions are present in numerous MC sequences at the same specific points, of which some are 3-fold symmetry related. Many of these frequent intron positions are also conserved in subfamilies or in groups of subfamilies transporting similar substrates. The analyses of the frequent and conserved intron positions in MCs suggest phylogenetic relationships not only between close but also distant homologs as well as a possible involvement of the intron positions in the evolution of the substrate specificity diversification of the MC family members.}, } @article {pmid36602189, year = {2023}, author = {Delling, B and Thörn, F and Norén, M and Irestedt, M}, title = {Museomics reveals the phylogenetic position of the extinct Moroccan trout Salmo pallaryi.}, journal = {Journal of fish biology}, volume = {102}, number = {3}, pages = {619-627}, doi = {10.1111/jfb.15299}, pmid = {36602189}, issn = {1095-8649}, mesh = {Animals ; Phylogeny ; *Trout/genetics ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Sequence Analysis, DNA ; }, abstract = {The authors used museomics to reconstruct the mitochondrial genome from two individuals of the Moroccan, endemic and extinct trout, Salmo pallaryi. They further obtained partial data from 21 nuclear genes previously used for trout phylogenetic analyses. Phylogenetic analyses, including publicly available data from the mitochondrial control region and the cytochrome b gene, and the 21 nuclear genes, place S. pallaryi among other North African trouts. mtDNA places S. pallaryi close to Salmo macrostigma within a single North African clade. Although the nuclear coverage of the genome was low, both specimens were independently positioned as sisters to one of two distantly related North African clades, viz. the Atlas clade with the Dades trout, Salmo multipunctatus. Phylogenetic discordance between mtDNA and nuclear DNA phylogenies is briefly discussed. As several specimens that were extracted failed to produce DNA of sufficient quality, the authors discuss potential reasons for the failure. They suggest that museum specimens in poor physical condition may be better for DNA extraction compared to better-preserved ones, possibly related to the innovation of formalin as a fixative before ethanol storage in the early 20th century.}, } @article {pmid36146890, year = {2023}, author = {Pierszalowski, SP and Steel, DJ and Gabriele, CM and Neilson, JL and Vanselow, PBS and Cedarleaf, JA and Straley, JM and Baker, CS}, title = {mtDNA heteroplasmy gives rise to a new maternal lineage in North Pacific humpback whales (Megaptera novaeangliae).}, journal = {The Journal of heredity}, volume = {114}, number = {1}, pages = {14-21}, pmid = {36146890}, issn = {1465-7333}, mesh = {Animals ; Female ; Cattle ; *Humpback Whale/genetics ; DNA, Mitochondrial/genetics ; Heteroplasmy ; Mitochondria/genetics ; Cetacea/genetics ; }, abstract = {Heteroplasmy in the mitochondrial genome offers a rare opportunity to track the evolution of a newly arising maternal lineage in populations of non-model species. Here, we identified a previously unreported mitochondrial DNA haplotype while assembling an integrated database of DNA profiles and photo-identification records from humpback whales in southeastern Alaska (SEAK). The haplotype, referred to as A8, was shared by only 2 individuals, a mature female with her female calf, and differed by only a single base pair from a common haplotype in the North Pacific, referred to as A-. To investigate the origins of the A8 haplotype, we reviewed n = 1,089 electropherograms (including replicate samples) of n = 710 individuals with A- haplotypes from an existing collection. From this review, we found 20 individuals with clear evidence of heteroplasmy for A-/A8 (parental/derived) haplotypes. Of these, 15 were encountered in SEAK, 4 were encountered on the Hawaiian breeding ground (the primary migratory destination for whales in SEAK), and 1 was encountered in the northern Gulf of Alaska. We used genotype exclusion and likelihood to identify one of the heteroplasmic females as the likely mother of the A8 cow and grandmother of the A8 calf, establishing the inheritance and germ-line fixation of the new haplotype from the parental heteroplasmy. The mutation leading to this heteroplasmy and the fixation of the A8 haplotype provide an opportunity to document the population dynamics and regional fidelity of a newly arising maternal lineage in a population recovering from exploitation.}, } @article {pmid36938916, year = {2023}, author = {Jiao, J and Wang, X and Wei, C and Zhao, Y}, title = {Bioinspired Electrode for the Production and Timely Separation of Nitrile and Hydrogen.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {}, number = {}, pages = {e2208044}, doi = {10.1002/smll.202208044}, pmid = {36938916}, issn = {1613-6829}, abstract = {Replacing electrocatalytic oxygen evolution reaction (OER) with amine oxidation reaction is adopted to boost clean and environment-friendly energy source hydrogen (H2) in water. However, the electrocatalytic reaction is severely restricted by the strong adsorption of product on the catalyst surface. Inspired by the cooperation of flavin adenine dinucleotide and mitochondria membrane in biological system, the catalysis-separation complex electrodes are introduced to promote the desorption of product and hinder its readsorption by applying polytetrafluoroethylene (PTFE)-separation membrane on the one side of electrode, which is benefit for the cleanness of active sites on the catalyst surface for the continuous production and timely separation of nitrile and hydrogen. With the intermolecular force between PTFE and nitrile, the nitrile droplets can be quickly desorbed and separated from catalyst surface of anode, and the size of nitrile droplets on the catalyst surface is only 0.23% to that without PTFE. As a result, the current at 1.49 VRHE from the catalyst with PTFE membrane is about 33 times to that of catalyst without PTFE after long-term operation. Moreover, the cathode with PTFE membrane also achieves the rapid desorption of H2 bubbles and stable cathodic current because of the strong absorption of PTFE to H2 .}, } @article {pmid36929911, year = {2023}, author = {Biot-Pelletier, D and Bettinazzi, S and Gagnon-Arsenault, I and Dubé, AK and Bédard, C and Nguyen, THM and Fiumera, HL and Breton, S and Landry, CR}, title = {Evolutionary trajectories are contingent on mitonuclear interactions.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msad061}, pmid = {36929911}, issn = {1537-1719}, abstract = {Critical mitochondrial functions, including cellular respiration, rely on frequently interacting components expressed from both the mitochondrial and nuclear genomes. The fitness of eukaryotic organisms depends on a tight collaboration between both genomes. In the face of an elevated rate of evolution in mtDNA, current models predict that maintenance of mitonuclear compatibility relies on compensatory evolution of the nuclear genome. Mitonuclear interactions would therefore exert an influence on evolutionary trajectories. One prediction from this model is that the same nuclear genome evolving with different mitochondrial haplotypes would follow distinct molecular paths towards higher fitness. To test this prediction, we submitted 1344 populations derived from seven mitonuclear genotypes of Saccharomyces cerevisiae to more than 300 generations of experimental evolution in conditions that either select for a mitochondrial function, or that do not strictly require respiration for survival. Performing high-throughput phenotyping and whole-genome sequencing on independently evolved individuals, we identified numerous examples of gene-level evolutionary convergence among populations with the same mitonuclear background. Phenotypic and genotypic data on strains derived from this evolution experiment identify the nuclear genome and the environment as the main determinants of evolutionary divergence, but also show a modulating role for the mitochondrial genome exerted both directly and via interactions with the two other components. We finally recapitulated a subset of prominent loss-of-function alleles in the ancestral backgrounds and confirmed a generalized pattern of mitonuclear-specific and highly epistatic fitness effects. Together, these results demonstrate how mitonuclear interactions can dictate evolutionary divergence of populations with identical starting nuclear genotypes.}, } @article {pmid36921696, year = {2023}, author = {Lee, C and Ruhlman, TA and Jansen, RK}, title = {Rate accelerations in plastid and mitochondrial genomes of Cyperaceae occur in the same clades.}, journal = {Molecular phylogenetics and evolution}, volume = {}, number = {}, pages = {107760}, doi = {10.1016/j.ympev.2023.107760}, pmid = {36921696}, issn = {1095-9513}, abstract = {Cyperaceae, the second largest family in the monocot order Poales, comprises more than 5,500 species and includes the genus Eleocharis with ∼ 250 species. A previous study of complete plastomes of two Eleocharis species documented extensive structural heteroplasmy, gene order changes, high frequency of dispersed repeats along with gene losses and duplications. To better understand the phylogenetic distribution of gene and intron content as well as rates and patterns of sequence evolution within and between mitochondrial and plastid genomes of Eleocharis and Cyperaceae, an additional 29 Eleocharis organelle genomes were sequenced and analyzed. Eleocharis experienced extensive gene loss in both genomes while loss of introns was mitochondria-specific. Eleocharis has higher rates of synonymous (dS) and nonsynonymous (dN) substitutions in the plastid and mitochondrion than most sampled angiosperms, and the pattern was distinct from other eudicot lineages with accelerated rates. Several clades showed higher dS and dN in mitochondrial genes than in plastid genes. Furthermore, nucleotide substitution rates of mitochondrial genes were significantly accelerated on the branch leading to Cyperaceae compared to most angiosperms. Mitochondrial genes of Cyperaceae exhibited dramatic loss of RNA editing sites and a negative correlation between RNA editing and dS values was detected among angiosperms. Mutagenic retroprocessing and dysfunction of DNA replication, repair and recombination genes are the most likely cause of striking rate accelerations and loss of edit sites and introns in Eleocharis and Cyperaceae organelle genomes.}, } @article {pmid36915058, year = {2023}, author = {Zumkeller, S and Knoop, V}, title = {Categorizing 161 plant (streptophyte) mitochondrial group II introns into 29 families of related paralogues finds only limited links between intron mobility and intron-borne maturases.}, journal = {BMC ecology and evolution}, volume = {23}, number = {1}, pages = {5}, pmid = {36915058}, issn = {2730-7182}, mesh = {Introns/genetics ; *Evolution, Molecular ; *Mitochondria/genetics ; Plants/genetics ; Cell Nucleus ; }, abstract = {Group II introns are common in the two endosymbiotic organelle genomes of the plant lineage. Chloroplasts harbor 22 positionally conserved group II introns whereas their occurrence in land plant (embryophyte) mitogenomes is highly variable and specific for the seven major clades: liverworts, mosses, hornworts, lycophytes, ferns, gymnosperms and flowering plants. Each plant group features "signature selections" of ca. 20-30 paralogues from a superset of altogether 105 group II introns meantime identified in embryophyte mtDNAs, suggesting massive intron gains and losses along the backbone of plant phylogeny. We report on systematically categorizing plant mitochondrial group II introns into "families", comprising evidently related paralogues at different insertion sites, which may even be more similar than their respective orthologues in phylogenetically distant taxa. Including streptophyte (charophyte) algae extends our sampling to 161 and we sort 104 streptophyte mitochondrial group II introns into 25 core families of related paralogues evidently arising from retrotransposition events. Adding to discoveries of only recently created intron paralogues, hypermobile introns and twintrons, our survey led to further discoveries including previously overlooked "fossil" introns in spacer regions or e.g., in the rps8 pseudogene of lycophytes. Initially excluding intron-borne maturase sequences for family categorization, we added an independent analysis of maturase phylogenies and find a surprising incongruence between intron mobility and the presence of intron-borne maturases. Intriguingly, however, we find that several examples of nuclear splicing factors meantime characterized simultaneously facilitate splicing of independent paralogues now placed into the same intron families. Altogether this suggests that plant group II intron mobility, in contrast to their bacterial counterparts, is not intimately linked to intron-encoded maturases.}, } @article {pmid36913593, year = {2023}, author = {Swainsbury, DJK and Hawkings, FR and Martin, EC and Musiał, S and Salisbury, JH and Jackson, PJ and Farmer, DA and Johnson, MP and Siebert, CA and Hitchcock, A and Hunter, CN}, title = {Cryo-EM structure of the four-subunit Rhodobacter sphaeroides cytochrome bc1 complex in styrene maleic acid nanodiscs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {12}, pages = {e2217922120}, doi = {10.1073/pnas.2217922120}, pmid = {36913593}, issn = {1091-6490}, mesh = {*Rhodobacter sphaeroides/chemistry ; Cytochromes c ; Cytochromes b ; Styrene ; Cryoelectron Microscopy ; Quinones ; Lipids ; Electron Transport Complex III ; Oxidation-Reduction ; }, abstract = {Cytochrome bc1 complexes are ubiquinol:cytochrome c oxidoreductases, and as such, they are centrally important components of respiratory and photosynthetic electron transfer chains in many species of bacteria and in mitochondria. The minimal complex has three catalytic components, which are cytochrome b, cytochrome c1, and the Rieske iron-sulfur subunit, but the function of mitochondrial cytochrome bc1 complexes is modified by up to eight supernumerary subunits. The cytochrome bc1 complex from the purple phototrophic bacterium Rhodobacter sphaeroides has a single supernumerary subunit called subunit IV, which is absent from current structures of the complex. In this work we use the styrene-maleic acid copolymer to purify the R. sphaeroides cytochrome bc1 complex in native lipid nanodiscs, which retains the labile subunit IV, annular lipids, and natively bound quinones. The catalytic activity of the four-subunit cytochrome bc1 complex is threefold higher than that of the complex lacking subunit IV. To understand the role of subunit IV, we determined the structure of the four-subunit complex at 2.9 Å using single particle cryogenic electron microscopy. The structure shows the position of the transmembrane domain of subunit IV, which lies across the transmembrane helices of the Rieske and cytochrome c1 subunits. We observe a quinone at the Qo quinone-binding site and show that occupancy of this site is linked to conformational changes in the Rieske head domain during catalysis. Twelve lipids were structurally resolved, making contacts with the Rieske and cytochrome b subunits, with some spanning both of the two monomers that make up the dimeric complex.}, } @article {pmid36883279, year = {2023}, author = {García Pascual, B and Nordbotten, JM and Johnston, IG}, title = {Cellular and environmental dynamics influence species-specific extents of organelle gene retention.}, journal = {Proceedings. Biological sciences}, volume = {290}, number = {1994}, pages = {20222140}, pmid = {36883279}, issn = {1471-2954}, mesh = {Species Specificity ; *Mitochondria ; *Eukaryotic Cells ; Eukaryota ; }, abstract = {Mitochondria and plastids rely on many nuclear-encoded genes, but retain small subsets of the genes they need to function in their own organelle DNA (oDNA). Different species retain different numbers of oDNA genes, and the reasons for these differences are not completely understood. Here, we use a mathematical model to explore the hypothesis that the energetic demands imposed by an organism's changing environment influence how many oDNA genes it retains. The model couples the physical biology of cell processes of gene expression and transport to a supply-and-demand model for the environmental dynamics to which an organism is exposed. The trade-off between fulfilling metabolic and bioenergetic environmental demands, and retaining genetic integrity, is quantified for a generic gene encoded either in oDNA or in nuclear DNA. Species in environments with high-amplitude, intermediate-frequency oscillations are predicted to retain the most organelle genes, whereas those in less dynamic or noisy environments the fewest. We discuss support for, and insight from, these predictions with oDNA data across eukaryotic taxa, including high oDNA gene counts in sessile organisms exposed to day-night and intertidal oscillations (including plants and algae) and low counts in parasites and fungi.}, } @article {pmid36882771, year = {2023}, author = {Bu, XL and Zhao, WS and Li, WX and Zou, H and Wu, SG and Li, M and Wang, GT}, title = {Mitochondrial metabolism of the facultative parasite Chilodonella uncinata (Alveolata, Ciliophora).}, journal = {Parasites & vectors}, volume = {16}, number = {1}, pages = {92}, pmid = {36882771}, issn = {1756-3305}, mesh = {Animals ; *Alveolata ; *Parasites ; Phylogeny ; *Ciliophora/genetics ; Mitochondria ; }, abstract = {BACKGROUND: Chilodonella uncinata is an aerobic ciliate capable of switching between being free-living and parasitic on fish fins and gills, causing tissue damage and host mortality. It is widely used as a model organism for genetic studies, but its mitochondrial metabolism has never been studied. Therefore, we aimed to describe the morphological features and metabolic characteristics of its mitochondria.

METHODS: Fluorescence staining and transmission electron microscopy (TEM) were used to observe the morphology of mitochondria. Single-cell transcriptome data of C. uncinata were annotated by the Clusters of Orthologous Genes (COG) database. Meanwhile, the metabolic pathways were constructed based on the transcriptomes. The phylogenetic analysis was also made based on the sequenced cytochrome c oxidase subunit 1 (COX1) gene.

RESULTS: Mitochondria were stained red using Mito-tracker Red staining and were stained slightly blue by DAPI dye. The cristae and double membrane structures of the mitochondria were observed by TEM. Besides, many lipid droplets were evenly distributed around the macronucleus. A total of 2594 unigenes were assigned to 23 functional classifications of COG. Mitochondrial metabolic pathways were depicted. The mitochondria contained enzymes for the complete tricarboxylic acid (TCA) cycle, fatty acid metabolism, amino acid metabolism, and cytochrome-based electron transport chain (ETC), but only partial enzymes involved in the iron-sulfur clusters (ISCs).

CONCLUSIONS: Our results showed that C. uncinata possess typical mitochondria. Stored lipid droplets inside mitochondria may be the energy storage of C. uncinata that helps its transmission from a free-living to a parasitic lifestyle. These findings also have improved our knowledge of the mitochondrial metabolism of C. uncinata and increased the volume of molecular data for future studies of this facultative parasite.}, } @article {pmid36469010, year = {2023}, author = {Penter, L and Ten Hacken, E and Southard, J and Lareau, CA and Ludwig, LS and Li, S and Neuberg, DS and Livak, KJ and Wu, CJ}, title = {Mitochondrial DNA Mutations as Natural Barcodes for Lineage Tracing of Murine Tumor Models.}, journal = {Cancer research}, volume = {83}, number = {5}, pages = {667-672}, pmid = {36469010}, issn = {1538-7445}, support = {R01 CA216273/CA/NCI NIH HHS/United States ; P01 CA206978/CA/NCI NIH HHS/United States ; R01 CA155010/CA/NCI NIH HHS/United States ; R50 CA251956/CA/NCI NIH HHS/United States ; R21 CA267527/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Chromatin ; Mutation ; *Neoplasms/genetics ; }, abstract = {UNLABELLED: Murine models are indispensable tools for functional genomic studies and preclinical testing of novel therapeutic approaches. Mitochondrial single-cell assay for transposase-accessible chromatin using sequencing (mtscATAC-seq) enables the dissection of cellular heterogeneity and clonal dynamics by capturing chromatin accessibility, copy-number variations (CNV), and mitochondrial DNA (mtDNA) mutations, yet its applicability to murine studies remains unexplored. By leveraging mtscATAC-seq in novel chronic lymphocytic leukemia and Richter syndrome mouse models, we report the detection of mtDNA mutations, particularly in highly proliferative murine cells, alongside CNV and chromatin state changes indicative of clonal evolution upon secondary transplant. This study thus demonstrates the feasibility and utility of multi-modal single-cell and natural barcoding approaches to characterize murine cancer models.

SIGNIFICANCE: mtDNA mutations can serve as natural barcodes to enable lineage tracing in murine cancer models, which can be used to provide new insights into disease biology and to identify therapeutic vulnerabilities.}, } @article {pmid36860172, year = {2023}, author = {Cantó-Santos, J and Valls-Roca, L and Tobías, E and García-García, FJ and Guitart-Mampel, M and Esteve-Codina, A and Martín-Mur, B and Casado, M and Artuch, R and Solsona-Vilarrasa, E and Fernandez-Checa, JC and García-Ruiz, C and Rentero, C and Enrich, C and Moreno-Lozano, PJ and Milisenda, JC and Cardellach, F and Grau-Junyent, JM and Garrabou, G}, title = {Unravelling inclusion body myositis using a patient-derived fibroblast model.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {}, number = {}, pages = {}, doi = {10.1002/jcsm.13178}, pmid = {36860172}, issn = {2190-6009}, abstract = {BACKGROUND: Inclusion body myositis (IBM) is an inflammatory myopathy clinically characterized by proximal and distal muscle weakness, with inflammatory infiltrates, rimmed vacuoles and mitochondrial changes in muscle histopathology. There is scarce knowledge on IBM aetiology, and non-established biomarkers or effective treatments are available, partly due to the lack of validated disease models.

METHODS: We have performed transcriptomics and functional validation of IBM muscle pathological hallmarks in fibroblasts from IBM patients (n = 14) and healthy controls (n = 12), paired by age and sex. The results comprise an mRNA-seq, together with functional inflammatory, autophagy, mitochondrial and metabolic changes between patients and controls.

RESULTS: Gene expression profile of IBM vs control fibroblasts revealed 778 differentially expressed genes (P-value adj < 0.05) related to inflammation, mitochondria, cell cycle regulation and metabolism. Functionally, an increased inflammatory profile was observed in IBM fibroblasts with higher supernatant cytokine secretion (three-fold increase). Autophagy was reduced considering basal protein mediators (18.4% reduced), time-course autophagosome formation (LC3BII 39% reduced, P-value < 0.05), and autophagosome microscopic evaluation. Mitochondria displayed reduced genetic content (by 33.9%, P-value < 0.05) and function (30.2%-decrease in respiration, 45.6%-decline in enzymatic activity (P-value < 0.001), 14.3%-higher oxidative stress, 135.2%-increased antioxidant defence (P-value < 0.05), 11.6%-reduced mitochondrial membrane potential (P-value < 0.05) and 42.8%-reduced mitochondrial elongation (P-value < 0.05)). In accordance, at the metabolite level, organic acid showed a 1.8-fold change increase, with conserved amino acid profile. Correlating to disease evolution, oxidative stress and inflammation emerge as potential markers of prognosis.

CONCLUSIONS: These findings confirm the presence of molecular disturbances in peripheral tissues from IBM patients and prompt patients' derived fibroblasts as a promising disease model, which may eventually be exported to other neuromuscular disorders. We additionally identify new molecular players in IBM associated with disease progression, setting the path to deepen in disease aetiology, in the identification of novel biomarkers or in the standardization of biomimetic platforms to assay new therapeutic strategies for preclinical studies.}, } @article {pmid36858654, year = {2023}, author = {Rubio-Tomás, T and Sotiriou, A and Tavernarakis, N}, title = {The interplay between selective types of (macro)autophagy: Mitophagy and xenophagy.}, journal = {International review of cell and molecular biology}, volume = {374}, number = {}, pages = {129-157}, doi = {10.1016/bs.ircmb.2022.10.003}, pmid = {36858654}, issn = {1937-6448}, abstract = {Autophagy is a physiological response, activated by a myriad of endogenous and exogenous cues, including DNA damage, perturbation of proteostasis, depletion of nutrients or oxygen and pathogen infection. Upon sensing those stimuli, cells employ multiple non-selective and selective autophagy pathways to promote fitness and survival. Importantly, there are a variety of selective types of autophagy. In this review we will focus on autophagy of bacteria (xenophagy) and autophagy of mitochondria (mitophagy). We provide a brief introduction to bulk autophagy, as well as xenophagy and mitophagy, highlighting their common molecular factors. We also describe the role of xenophagy and mitophagy in the detection and elimination of pathogens by the immune system and the adaptive mechanisms that some pathogens have developed through evolution to escape the host autophagic response. Finally, we summarize the recent articles (from the last five years) linking bulk autophagy with xenophagy and/or mitophagy in the context on developmental biology, cancer and metabolism.}, } @article {pmid36858653, year = {2023}, author = {Degli Esposti, M}, title = {The bacterial origin of mitochondria: Incorrect phylogenies and the importance of metabolic traits.}, journal = {International review of cell and molecular biology}, volume = {374}, number = {}, pages = {1-35}, doi = {10.1016/bs.ircmb.2022.11.001}, pmid = {36858653}, issn = {1937-6448}, abstract = {This article provides an updated review on the evolution of mitochondria from bacteria, which were likely related to extant alphaproteobacteria. Particular attention is given to the timeline of oxygen history on Earth and the entwined phases of eukaryotic evolution that produced the animals that still populate our planet. Mitochondria of early-branching unicellular eukaryotes and plants appear to retain partial or vestigial traits that were directly inherited from the alphaproteobacterial ancestors of the organelles. Most of such traits define the current aerobic physiology of mitochondria. Conversely, the anaerobic traits that would be essential in the syntrophic associations postulated for the evolution of eukaryotic cells are scantly present in extant alphaproteobacteria, and therefore cannot help defining from which bacterial lineage the ancestors of mitochondria originated. This question has recently been addressed quantitatively, reaching the novel conclusion that marine bacteria related to Iodidimonas may be the living relatives of protomitochondria. Additional evidence is presented that either support or does not contrast this novel view of the bacterial origin of mitochondria.}, } @article {pmid36835385, year = {2023}, author = {Yang, JX and Dierckxsens, N and Bai, MZ and Guo, YY}, title = {Multichromosomal Mitochondrial Genome of Paphiopedilum micranthum: Compact and Fragmented Genome, and Rampant Intracellular Gene Transfer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835385}, issn = {1422-0067}, mesh = {*Genome, Mitochondrial ; DNA, Mitochondrial ; Mitochondria/genetics ; *Magnoliopsida/genetics ; *Orchidaceae/genetics ; Phylogeny ; }, abstract = {Orchidaceae is one of the largest families of angiosperms. Considering the large number of species in this family and its symbiotic relationship with fungi, Orchidaceae provide an ideal model to study the evolution of plant mitogenomes. However, to date, there is only one draft mitochondrial genome of this family available. Here, we present a fully assembled and annotated sequence of the mitochondrial genome (mitogenome) of Paphiopedilum micranthum, a species with high economic and ornamental value. The mitogenome of P. micranthum was 447,368 bp in length and comprised 26 circular subgenomes ranging in size from 5973 bp to 32,281 bp. The genome encoded for 39 mitochondrial-origin, protein-coding genes; 16 tRNAs (three of plastome origin); three rRNAs; and 16 ORFs, while rpl10 and sdh3 were lost from the mitogenome. Moreover, interorganellar DNA transfer was identified in 14 of the 26 chromosomes. These plastid-derived DNA fragments represented 28.32% (46,273 bp) of the P. micranthum plastome, including 12 intact plastome origin genes. Remarkably, the mitogenome of P. micranthum and Gastrodia elata shared 18% (about 81 kb) of their mitochondrial DNA sequences. Additionally, we found a positive correlation between repeat length and recombination frequency. The mitogenome of P. micranthum had more compact and fragmented chromosomes compared to other species with multichromosomal structures. We suggest that repeat-mediated homologous recombination enables the dynamic structure of mitochondrial genomes in Orchidaceae.}, } @article {pmid36720422, year = {2023}, author = {Baltazar-Soares, M and Karell, P and Wright, D and Nilsson, JÅ and Brommer, JE}, title = {Bringing to light nuclear-mitochondrial insertions in the genomes of nocturnal predatory birds.}, journal = {Molecular phylogenetics and evolution}, volume = {181}, number = {}, pages = {107722}, doi = {10.1016/j.ympev.2023.107722}, pmid = {36720422}, issn = {1095-9513}, mesh = {Animals ; Phylogeny ; *Mitochondria/genetics ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; Birds/genetics ; Sequence Analysis, DNA ; Cell Nucleus/genetics ; }, abstract = {Mito-nuclear insertions, or NUMTs, relate to genetic material of mitochondrial origin that have been transferred to the nuclear DNA molecule. The increasing amounts of genomic data currently being produced presents an opportunity to investigate this type of patterns in genome evolution of non-model organisms. Identifying NUMTs across a range of closely related taxa allows one to generalize patterns of insertion and maintenance in autosomes, which is ultimately relevant to the understanding of genome biology and evolution. Here we collected existing pairwise genome-mitogenome data of the order Strigiformes, a group that includes all the nocturnal bird predators. We identified NUMTs by applying percent similarity thresholds after blasting mitochondrial genomes against nuclear genome assemblies. We identified NUMTsin all genomes with numbers ranging from 4 in Bubo bubo to 24 in Ciccaba nigrolineata. Statistical analyses revealed NUMT size to negatively correlate with NUMT's sequence similarity to with original mtDNA region. Lastly, characterizing these nuclear insertions of mitochondrial origin in a comparative genomics framework produced variable phylogenetic patterns, suggesting in some cases that insertions might pre-date speciation events within Strigiformes.}, } @article {pmid36838260, year = {2023}, author = {Fuerst, PA}, title = {The Status of Molecular Analyses of Isolates of Acanthamoeba Maintained by International Culture Collections.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, doi = {10.3390/microorganisms11020295}, pmid = {36838260}, issn = {2076-2607}, abstract = {Acanthamoeba is among the most ubiquitous protistan groups in nature. Knowledge of the biological diversity of Acanthamoeba comes in part from the use of strains maintained by the major microbial culture collections, ATCC and CCAP. Standard strains are vital to ensure the comparability of research. The diversity of standard strains of Acanthamoeba in the culture collections is reviewed, emphasizing the extent of genotypic studies based on DNA sequencing of the small subunit ribosomal RNA from the nucleus (18S rRNA gene; Rns) or the mitochondria (16S-like rRNA gene; rns). Over 170 different strains have been maintained at some time by culture centers. DNA sequence information is available for more than 70% of these strains. Determination of the genotypic classification of standard strains within the genus indicates that frequencies of types within culture collections only roughly mirror that from clinical or environmental studies, with significant differences in the frequency of some genotypes. Culture collections include the type of isolate from almost all named species of Acanthamoeba, allowing an evaluation of the validity of species designations. Multiple species are found to share the same Sequence Type, while multiple Sequence Types have been identified for different strains that share the same species name. Issues of sequence reliability and the possibility that a small number of standard strains have been mislabeled when studied are also examined, leading to potential problems for comparative analyses. It is important that all species have reliable genotype designations. The culture collections should be encouraged to assist in completing the molecular inventory of standard strains, while workers in the Acanthamoeba research community should endeavor to ensure that strains representative of genotypes that are missing from the culture collection are provided to the culture centers for preservation.}, } @article {pmid36831240, year = {2023}, author = {Fang, Y and Zhang, F and Zhan, Y and Lu, M and Xu, D and Wang, J and Li, Q and Zhao, L and Su, Y}, title = {RpS3 Is Required for Spermatogenesis of Drosophila melanogaster.}, journal = {Cells}, volume = {12}, number = {4}, pages = {}, doi = {10.3390/cells12040573}, pmid = {36831240}, issn = {2073-4409}, abstract = {Ribosomal proteins (RPs) constitute the ribosome, thus participating in the protein biosynthesis process. Emerging studies have suggested that many RPs exhibit different expression levels across various tissues and function in a context-dependent manner for animal development. Drosophila melanogaster RpS3 encodes the ribosomal protein S3, one component of the 40S subunit of ribosomes. We found that RpS3 is highly expressed in the reproductive organs of adult flies and its depletion in male germline cells led to severe defects in sperm production and male fertility. Immunofluorescence staining showed that RpS3 knockdown had little effect on early germ cell differentiation, but strongly disrupted the spermatid elongation and individualization processes. Furthermore, we observed abnormal morphology and activity of mitochondrial derivatives in the elongating spermatids of RpS3-knockdown testes, which could cause the failure of axoneme elongation. We also found that RpS3 RNAi inhibited the formation of the individualization complex that takes charge of disassociating the spermatid bundle. In addition, excessive apoptotic cells were detected in the RpS3-knockdown testes, possibly to clean the defective spermatids. Together, our data demonstrated that RpS3 plays an important role in regulating spermatid elongation and individualization processes and, therefore, is required for normal Drosophila spermatogenesis.}, } @article {pmid36822346, year = {2023}, author = {Cheng, A and Zhang, Y and Sun, J and Huang, D and Sulaiman, JE and Huang, X and Wu, L and Ye, W and Wu, C and Lam, HN and Shi, Y and Qian, PY}, title = {Pterosin sesquiterpenoids from Pteris laeta Wall. ex Ettingsh. Protect cells from glutamate excitotoxicity by modulating mitochondrial signals.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {116308}, doi = {10.1016/j.jep.2023.116308}, pmid = {36822346}, issn = {1872-7573}, abstract = {The genus Pteris (Pteridaceae) has been used as a traditional herb for a long time. In particular, Pteris laeta Wall. ex Ettingsh. has been widely used in traditional Chinese medicine to treat nervous system diseases and some pterosin sesquiterpenes from Pteris show neuroprotective bioactivity, but their underlying molecular mechanisms remain elusive. Therefore, to investigate the neuroprotective activity and working mechanism of pterosin sesquiterpenes from P. laeta Wall. ex Ettingsh. will provide a better understanding and guidance in using P. laeta Wall. ex Ettingsh. as a traditional Chinese medicine.

AIM OF THE STUDY: We aim to develop effective treatments for neurodegenerative diseases from pterosin sesquiterpenes by evaluating their neuroprotective activity and investigating their working mechanisms.

MATERIALS AND METHODS: Primary screening on the glutamate-induced excitotoxicity cell model was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Fluorescent-activated cell sorting (FACS) was used to analyze the activation level of glutamate receptors and mitochondria membrane potential after treatment. Transcriptomics and proteomics analysis was performed to identify possible targets of pterosin B. The key pathways were enriched by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis through the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The core targets were visualized by a protein-protein interaction network using STRING. The mRNA and protein expressions were evaluated using real-time quantitative polymerase chain reaction (Q-PCR) and western blot, respectively. Immunocytochemistry was performed to monitor mitochondrial and apoptotic proteins. Cellular reactive oxygen species (ROS) were measured by ROS assay, and Ca[2+] was stained with Fluo-4 AM to quantify intracellular Ca[2+] levels.

RESULTS: We found pterosin B from Pteris laeta Wall. ex Ettingsh. showed significant neuroprotective activity against glutamate excitotoxicity, enhancing cell viability from 43.8% to 105% (p-value: <0.0001). We demonstrated that pterosin B worked on the downstream signaling pathways of glutamate excitotoxicity rather than directly blocking the activation of glutamate receptors. Pterosin B restored mitochondria membrane potentials, alleviated intracellular calcium overload from 107.4% to 95.47% (p-value: 0.0006), eliminated cellular ROS by 36.55% (p-value: 0.0143), and partially secured cells from LPS-induced inflammation by increasing cell survival from 46.75% to 58.5% (p-value: 0.0114). Notably, pterosin B enhanced the expression of nuclear factor-erythroid factor 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) by 2.86-fold (p-value: 0.0006) and 4.24-fold (p-value: 0.0012), and down-regulated Kelch-like ECH-associated protein 1 (KEAP1) expression by 2.5-fold (p-value: 0.0107), indicating that it possibly promotes mitochondrial biogenesis and mitophagy to maintain mitochondria quality control and homeostasis, and ultimately inhibits apoptotic cell death.

CONCLUSIONS: Our work revealed that pterosin B protected cells from glutamate excitotoxicity by targeting the downstream mitochondrial signals, making it a valuable candidate for developing potential therapeutic agents in treating neurodegenerative diseases.}, } @article {pmid36810648, year = {2023}, author = {Li, Y and Chen, L and Si, L and Yang, Y and Zhou, C and Yu, F and Xia, G and Wang, H}, title = {Triphenylamine-equipped 1,8-naphthaolactam: a versatile scaffold for the custom design of efficient subcellular imaging agents.}, journal = {Journal of materials chemistry. B}, volume = {}, number = {}, pages = {}, doi = {10.1039/d2tb02528k}, pmid = {36810648}, issn = {2050-7518}, abstract = {Fluorescence imaging has enabled much progress in biological fields, while the evolution of commercially available dyes has lagged behind their advanced applications. Herein, we launch triphenylamine-equipped 1,8-naphthaolactam (NP-TPA) as a versatile scaffold for the custom design of an efficient subcellular imaging agent (NP-TPA-Tar), given its bright and constant emissions in various states, significant Stokes shifts, and facile modifiability. The resultant four NP-TPA-Tars maintain excellent emission behavior with targeted modifications and can map the spatial distribution of lysosomes, mitochondria, endoplasmic reticulum, and plasma membrane in Hep G2 cells. Compared to its commercial counterpart, NP-TPA-Tar has a 2.8-25.2 fold increase in Stokes shift, a 1.2-1.9 fold increase in photostability, enhanced targeting capability, and comparable imaging efficiency even at low concentrations of 50 nM. This work will help to accelerate the update of current imaging agents and super-resolution and real-time imaging in biological applications.}, } @article {pmid36806940, year = {2023}, author = {Rivera-Colón, AG and Rayamajhi, N and Fazal Minhas, B and Madrigal, G and Bilyk, KT and Yoon, V and Hüne, M and Gregory, S and Cheng, CC and Catchen, JM}, title = {Genomics of Secondarily Temperate Adaptation in the Only Non-Antarctic Icefish.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msad029}, pmid = {36806940}, issn = {1537-1719}, abstract = {White-blooded Antarctic icefishes, a family within the adaptive radiation of Antarctic notothenioid fishes, are an example of extreme biological specialization to both the chronic cold of the Southern Ocean and life without hemoglobin. As a result, icefishes display derived physiology that limits them to the cold and highly oxygenated Antarctic waters. Against these constraints, remarkably one species, the pike icefish Champsocephalus esox, successfully colonized temperate South American waters. To study the genetic mechanisms underlying secondarily temperate adaptation in icefishes, we generated chromosome-level genome assemblies of both C. esox and its Antarctic sister species, Champsocephalus gunnari. The C. esox genome is similar in structure and organization to that of its Antarctic congener; however, we observe evidence of chromosomal rearrangements coinciding with regions of elevated genetic divergence in pike icefish populations. We also find several key biological pathways under selection, including genes related to mitochondria and vision, highlighting candidates behind temperate adaptation in C. esox. Substantial antifreeze glycoprotein (AFGP) pseudogenization has occurred in the pike icefish, likely due to relaxed selection following ancestral escape from Antarctica. The canonical AFGP locus organization is conserved in C. esox and C. gunnari, but both show a translocation of two AFGP copies to a separate locus, previously unobserved in cryonotothenioids. Altogether, the study of this secondarily temperate species provides an insight into the mechanisms underlying adaptation to ecologically disparate environments in this otherwise highly specialized group.}, } @article {pmid36795453, year = {2023}, author = {Dong, LF and Rohlena, J and Zobalova, R and Nahacka, Z and Rodriguez, AM and Berridge, MV and Neuzil, J}, title = {Mitochondria on the move: Horizontal mitochondrial transfer in disease and health.}, journal = {The Journal of cell biology}, volume = {222}, number = {3}, pages = {}, doi = {10.1083/jcb.202211044}, pmid = {36795453}, issn = {1540-8140}, mesh = {Animals ; Phylogeny ; *Mitochondria/metabolism ; *Neoplasms/genetics/metabolism ; Energy Metabolism ; Mammals ; }, abstract = {Mammalian genes were long thought to be constrained within somatic cells in most cell types. This concept was challenged recently when cellular organelles including mitochondria were shown to move between mammalian cells in culture via cytoplasmic bridges. Recent research in animals indicates transfer of mitochondria in cancer and during lung injury in vivo, with considerable functional consequences. Since these pioneering discoveries, many studies have confirmed horizontal mitochondrial transfer (HMT) in vivo, and its functional characteristics and consequences have been described. Additional support for this phenomenon has come from phylogenetic studies. Apparently, mitochondrial trafficking between cells occurs more frequently than previously thought and contributes to diverse processes including bioenergetic crosstalk and homeostasis, disease treatment and recovery, and development of resistance to cancer therapy. Here we highlight current knowledge of HMT between cells, focusing primarily on in vivo systems, and contend that this process is not only (patho)physiologically relevant, but also can be exploited for the design of novel therapeutic approaches.}, } @article {pmid36327950, year = {2023}, author = {Filimonova, S}, title = {Fine structure of the posterior midgut in the mite Anystis baccarum (L.).}, journal = {Arthropod structure & development}, volume = {72}, number = {}, pages = {101218}, doi = {10.1016/j.asd.2022.101218}, pmid = {36327950}, issn = {1873-5495}, mesh = {Animals ; *Mites/ultrastructure ; Phylogeny ; Digestive System/ultrastructure ; *Arachnida ; Epithelial Cells ; }, abstract = {Homology of the posterior midgut regions (PMG) in different phylogenetic lineages of acariform mites (superorder Acariformes) remains unresolved. In the order Trombidiformes, the ultrastructure of the PMG is known primarily in derived groups; thus this study focuses on species belonging to a relatively basal trombidiform family. PMG of Anystis baccarum consists of the colon and postcolon separated by a small intercolon. The fine structure of the colon and postcolon is close to that of the corresponding organs of sarcoptiform mites with the epithelium showing absorptive and endocytotic activity. The epithelial cells produce a variety of excretory vacuoles and a peritrophic matrix around the feces. Morover, the epithelium of the postcolon is characterized by the highest apical brush border and especially numerous mitochondria suggesting involvement in water and ion absorption. The intercolon functions as a sphincter lined with an epithelium capable of producing excretory granules. A pair of short blind extensions arises assimmetrically from the intercolon into the body cavity. Ultrastructurally, these extensions are similar to the arachnid Malpighian tubules and may be their reduced version. Rare endocrine-like cells have been observed in the colon and postcolon.}, } @article {pmid36797268, year = {2023}, author = {Preston, AJ and Rogers, A and Sharp, M and Mitchell, G and Toruno, C and Barney, BB and Donovan, LN and Bly, J and Kennington, R and Payne, E and Iovino, A and Furukawa, G and Robinson, R and Shamloo, B and Buccilli, M and Anders, R and Eckstein, S and Fedak, EA and Wright, T and Maley, CC and Kiso, WK and Schmitt, D and Malkin, D and Schiffman, JD and Abegglen, LM}, title = {Elephant TP53-RETROGENE 9 induces transcription-independent apoptosis at the mitochondria.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {66}, pmid = {36797268}, issn = {2058-7716}, abstract = {Approximately 20 TP53 retrogenes exist in the African and Asian elephant genomes (Loxodonta Africana, Elephas Maximus) in addition to a conserved TP53 gene that encodes a full-length protein. Elephant TP53-RETROGENE 9 (TP53-R9) encodes a p53 protein (p53-R9) that is truncated in the middle of the canonical DNA binding domain. This C-terminally truncated p53 retrogene protein lacks the nuclear localization signals and oligomerization domain of its full-length counterpart. When expressed in human osteosarcoma cells (U2OS), p53-R9 binds to Tid1, the chaperone protein responsible for mitochondrial translocation of human p53 in response to cellular stress. Tid1 expression is required for p53-R9-induced apoptosis. At the mitochondria, p53-R9 binds to the pro-apoptotic BCL-2 family member Bax, which leads to caspase activation, cytochrome c release, and cell death. Our data show, for the first time, that expression of this truncated elephant p53 retrogene protein induces apoptosis in human cancer cells. Understanding the molecular mechanism by which the additional elephant TP53 retrogenes function may provide evolutionary insight that can be utilized for the development of therapeutics to treat human cancers.}, } @article {pmid36789533, year = {2023}, author = {Nagarajan-Radha, V and Beekman, M}, title = {G × G × E effect on phenotype expression in a non-conventional model organism, the unicellular slime mould Physarum polycephalum.}, journal = {Biology letters}, volume = {19}, number = {2}, pages = {20220494}, doi = {10.1098/rsbl.2022.0494}, pmid = {36789533}, issn = {1744-957X}, mesh = {*Physarum polycephalum/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Plasmids ; Phenotype ; }, abstract = {In metazoans, the expression of key phenotypic traits is sensitive to two- and three-way interactions between variation in mitochondrial DNA, nuclear DNA and the external environment. Whether gene-by-environment interactions affect phenotypes in single-celled eukaryotes is poorly studied, except in a few species of yeast and fungi. We developed a genetic panel of the unicellular slime mould, Physarum polycephalum containing strains differing in mitochondrial and nuclear DNA haplotypes. The panel also included two strains harbouring a selfishly replicating mitochondrial-fusion (mF) plasmid that could affect phenotype expression. We assayed movement and growth rate differences among the strains across two temperature regimes: 24° and 28°C. We found that the slime mould's growth rate, but not movement, is affected by G × G × E interactions. Predictably, mtDNA × nDNA interactions significantly affected both traits. The inter-trait correlation across the strains in each temperature regime was positive. Surprisingly, the mF plasmid had no negative effects on our chosen traits. Our study is the first to demonstrate genetic regulation of phenotype expression in a unicellular slime mould. The genetic effect on phenotypes manifests via epistatic interactions with the thermal environment, thus shedding new light on the role of G × G × E interactions in trait evolution in protists.}, } @article {pmid36787792, year = {2022}, author = {Broccard, N and Silva, NM and Currat, M}, title = {Simulated patterns of mitochondrial diversity are consistent with partial population turnover in Bronze Age Central Europe.}, journal = {American journal of biological anthropology}, volume = {177}, number = {1}, pages = {134-146}, pmid = {36787792}, issn = {2692-7691}, support = {31003A_182577/SNSF_/Swiss National Science Foundation/Switzerland ; 31003A_156853/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {*Mitochondria/genetics ; Europe ; *DNA, Mitochondrial/genetics ; Emigration and Immigration ; Biological Evolution ; DNA, Ancient ; }, abstract = {OBJECTIVES: The analysis of ancient mitochondrial DNA from osteological remains has challenged previous conclusions drawn from the analysis of mitochondrial DNA from present populations, notably by revealing an absence of genetic continuity between the Neolithic and modern populations in Central Europe. Our study investigates how to reconcile these contradictions at the mitochondrial level using a modeling approach.

MATERIALS AND METHODS: We used a spatially explicit computational framework to simulate ancient and modern DNA sequences under various evolutionary scenarios of post Neolithic demographic events and compared the genetic diversity of the simulated and observed mitochondrial sequences. We investigated which-if any-scenarios were able to reproduce statistics of genetic diversity similar to those observed, with a focus on the haplogroup N1a, associated with the spread of early Neolithic farmers.

RESULTS: Demographic fluctuations during the Neolithic transition or subsequent demographic collapses after this period, that is, due to epidemics such as plague, are not sufficient to explain the signal of population discontinuity detected on the mitochondrial DNA in Central Europe. Only a scenario involving a substantial genetic input due to the arrival of migrants after the Neolithic transition, possibly during the Bronze Age, is compatible with observed patterns of genetic diversity.

DISCUSSION: Our results corroborate paleogenomic studies, since out of the alternative hypotheses tested, the best one that was able to recover observed patterns of mitochondrial diversity in modern and ancient Central European populations was one were immigration of populations from the Pontic steppes during the Bronze Age was explicitly simulated.}, } @article {pmid36790303, year = {2023}, author = {Sokolova, IM}, title = {Ectotherm mitochondrial economy and responses to global warming.}, journal = {Acta physiologica (Oxford, England)}, volume = {}, number = {}, pages = {e13950}, doi = {10.1111/apha.13950}, pmid = {36790303}, issn = {1748-1716}, abstract = {Temperature is a key abiotic factor affecting ecology, biogeography and evolution of species. Alterations of energy metabolism play an important role in adaptations and plastic responses to temperature shifts on different time scales. Mitochondrial metabolism plays a key role in bioenergetics and redox balance making these organelles an important determinant of organismal performances such as growth, locomotion or development. Here I analyze the impacts of environmental temperature on the mitochondrial functions (including oxidative phosphorylation, proton leak, production of reactive oxygen species and ATP synthesis) of ectotherms and discuss the mechanisms underlying negative shifts in the mitochondrial energy economy caused by supraoptimal temperatures. Due to the differences in the thermal sensitivity of different mitochondrial processes, elevated temperatures (beyond the species- and population-specific optimal range) cause reallocation of the electron flux and the protonmotive force (Δp) in a way that decreases ATP synthesis efficiency, elevates the relative cost of the mitochondrial maintenance, causes excessive production of reactive oxygen species (ROS) and raises energy cost for antioxidant defense. These shifts in the mitochondrial energy economy might have negative consequences for the organismal fitness traits such as the thermal tolerance or growth. Correlation between the thermal sensitivity indices of the mitochondria and the whole organism indicate that these traits experience similar selective pressures but further investigations are needed to establish whether there is a cause-effect relationship between the mitochondrial failure and loss of organismal performance during temperature change.}, } @article {pmid36790104, year = {2023}, author = {Onuț-Brännström, I and Stairs, CW and Campos, KIA and Hiltunen Thorén, M and Ettema, TJG and Keeling, PJ and Bass, D and Burki, F}, title = {A mitosome with distinct metabolism in the uncultured protist parasite Paramikrocytos canceri (Rhizaria, Ascetosporea).}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evad022}, pmid = {36790104}, issn = {1759-6653}, abstract = {Ascetosporea are endoparasites of marine invertebrates that include economically important pathogens of aquaculture species. Owing to their often-minuscule cell sizes, strict intracellular lifestyle, lack of cultured representatives and minimal availability of molecular data, these unicellular parasites remain poorly studied. Here, we sequenced and assembled the genome and transcriptome of Paramikrocytos canceri, an endoparasite isolated from the European edible crab Cancer pagurus. Using bioinformatic predictions, we show that P. canceri likely possesses a mitochondrion-related organelle (MRO) with highly reduced metabolism, resembling the mitosomes of other parasites but with key differences. Like other mitosomes, this MRO is predicted to have reduced metabolic capacity and lack an organellar genome and function in iron-sulfur cluster (ISC) pathway-mediated Fe-S cluster biosynthesis. However, the MRO in P. canceri is uniquely predicted to produce ATP via a partial glycolytic pathway and synthesize phospholipids de novo through the CDP-DAG pathway. Heterologous gene expression confirmed that proteins from the ISC and CDP-DAG pathways retain mitochondrial targeting sequences that are recognized by yeast mitochondria. This represents a unique combination of metabolic pathways in an MRO, including the first reported case of a mitosome-like organelle able to synthesize phospholipids de novo. Some of these phospholipids, such as phosphatidylserine, are vital in other protist endoparasites that invade their host through apoptotic mimicry.}, } @article {pmid36787420, year = {2023}, author = {Zheng, Y and Ye, Z and Xiao, Y}, title = {Subtle Structural Translation Magically Modulates the Super-Resolution Imaging of Self-Blinking Rhodamines.}, journal = {Analytical chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.analchem.2c05298}, pmid = {36787420}, issn = {1520-6882}, abstract = {The evolution of super-resolution imaging techniques is benefited from the ongoing competition for optimal rhodamine fluorophores. Yet, it seems blind to construct the desired rhodamine molecule matching the imaging need without the knowledge on imaging impact of even the minimum structural translation. Herein, we have designed a pair of self-blinking sulforhodamines (STMR and SRhB) with the bare distinction of methyl or ethyl substituents and engineered them with Halo protein ligands. Although the two possess similar spectral properties (λab, λfl, ϕ, etc.), they demonstrated unique single-molecule characteristics preferring to individual imaging applications. Experimentally, STMR with high emissive rates was qualified for imaging structures with rapid dynamics (endoplasmic reticulum, and mitochondria), and SRhB with prolonged on-times and photostability was suited for relatively "static" nuclei and microtubules. Using this new knowledge, the mitochondrial morphology during apoptosis and ferroptosis was first super-resolved by STMR. Our study highlights the significance of even the smallest structural modification to the modulation of super-resolution imaging performance and would provide insights for future fluorophore design.}, } @article {pmid36782130, year = {2023}, author = {Zhang, S and Wang, J and He, W and Kan, S and Liao, X and Jordan, DR and Mace, ES and Tao, Y and Cruickshank, AW and Klein, R and Yuan, D and Tembrock, LR and Wu, Z}, title = {Variation in mitogenome structural conformation in wild and cultivated lineages of sorghum corresponds with domestication history and plastome evolution.}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {91}, pmid = {36782130}, issn = {1471-2229}, abstract = {BACKGROUND: Mitochondria are organelles within eukaryotic cells that are central to the metabolic processes of cellular respiration and ATP production. However, the evolution of mitochondrial genomes (mitogenomes) in plants is virtually unknown compared to animal mitogenomes or plant plastids, due to complex structural variation and long stretches of repetitive DNA making accurate genome assembly more challenging. Comparing the structural and sequence differences of organellar genomes within and between sorghum species is an essential step in understanding evolutionary processes such as organellar sequence transfer to the nuclear genome as well as improving agronomic traits in sorghum related to cellular metabolism.

RESULTS: Here, we assembled seven sorghum mitochondrial and plastid genomes and resolved reticulated mitogenome structures with multilinked relationships that could be grouped into three structural conformations that differ in the content of repeats and genes by contig. The grouping of these mitogenome structural types reflects the two domestication events for sorghum in east and west Africa.

CONCLUSIONS: We report seven mitogenomes of sorghum from different cultivars and wild sources. The assembly method used here will be helpful in resolving complex genomic structures in other plant species. Our findings give new insights into the structure of sorghum mitogenomes that provides an important foundation for future research into the improvement of sorghum traits related to cellular respiration, cytonuclear incompatibly, and disease resistance.}, } @article {pmid36724679, year = {2023}, author = {Rivero, J and Cutillas, C and Callejón, R}, title = {New genetic lineage of whipworm present in Bactrian camel (Camelus bactrianus).}, journal = {Veterinary parasitology}, volume = {315}, number = {}, pages = {109886}, doi = {10.1016/j.vetpar.2023.109886}, pmid = {36724679}, issn = {1873-2550}, mesh = {Animals ; *Camelus/parasitology ; Trichuris/genetics ; Bayes Theorem ; Phylogeny ; Mitochondria ; *Parasites ; }, abstract = {With a global population of around 35 million in 47 countries, camels play a crucial role in the economy of many marginal and desert areas of the world where they survive in harsh conditions. Nonetheless, there is insufficient knowledge regarding camels' parasite fauna which can reduce their milk and meat production. A molecular study for the Trichuris population of Camelus bactrianus from Spain is presented based on sequences of mitochondrial (cox1, cob, rrnL) and ribosomal (ITS1 and ITS2) DNA regions. Bayesian Inference and Maximum Likelihood methods were used to infer phylogenies for (i) each gene separately, (ii) the combined mitochondrial data, and (iii) the combined mitochondrial and ribosomal dataset. Molecular analyses revealed the existence of two different genetic lineages in the Trichuris parasites populations of C. bactrianus. Future studies should focus on whether there is a coevolution process corresponding to the wild or domestic character of C. bactrianus and Camelus dromedarius. Furthermore, it is necessary to increase integrative taxonomic studies on Trichuris spp. based on morphological, biometric, and molecular data, which will inevitably contribute to our knowledge of the etiology of trichuriasis.}, } @article {pmid36657651, year = {2023}, author = {Moreno-Carmona, M and Montaña-Lozano, P and Prada Quiroga, CF and Baeza, JA}, title = {Comparative analysis of mitochondrial genomes reveals family-specific architectures and molecular features in scorpions (Arthropoda: Arachnida: Scorpiones).}, journal = {Gene}, volume = {859}, number = {}, pages = {147189}, doi = {10.1016/j.gene.2023.147189}, pmid = {36657651}, issn = {1879-0038}, mesh = {Humans ; Animals ; Scorpions/genetics ; *Arachnida/genetics ; *Genome, Mitochondrial/genetics ; Phylogeny ; Mitochondria/genetics ; RNA, Transfer/genetics ; }, abstract = {Scorpions are a group of arachnids with great evolutionary success that comprise more than 2,000 described species. Mitochondrial genomes have been little studied in this clade. We describe and compare different scorpion mitochondrial genomes and analyze their architecture and molecular characteristics. We assembled eight new scorpion mitochondrial genomes from transcriptomic datasets, annotated them, predicted the secondary structures of tRNAs, and compared the nucleotide composition, codon usage, and relative synonymous codon usage of 16 complete scorpion mitochondrial genomes. Lastly, we provided a phylogeny based on all mitochondrial protein coding genes. We characterized the mitogenomes in detail and reported particularities such as dissimilar synteny in the family Buthidae compared to other scorpions, unusual tRNA secondary structures, and unconventional start and stop codons in all scorpions. Our comparative analysis revealed that scorpion mitochondrial genomes exhibit different architectures and features depending on taxonomic identity. We highlight the parvorder Buthida, particularly the family Buthidae, as it invariably exhibited different mitogenome features such as synteny, codon usage, and AT-skew compared to the parvorder Iurida that included the rest of the scorpion families we analyzed in this study. Our results provide a better understanding of the evolution of mitogenome features and phylogenetic relationships in scorpions.}, } @article {pmid36759539, year = {2023}, author = {Kise, H and Iguchi, A and Ikegami, T and Onishi, Y and Goto, K and Tanaka, Y and Washburn, TW and Nishijima, M and Kunishima, T and Okamoto, N and Suzuki, A}, title = {Genetic population structures of common scavenging species near hydrothermal vents in the Okinawa Trough.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2348}, pmid = {36759539}, issn = {2045-2322}, mesh = {Animals ; *Hydrothermal Vents ; Phylogeny ; Genetics, Population ; *Decapoda ; Mitochondria/genetics ; Ecosystem ; }, abstract = {Deep-sea mining of hydrothermal deposits off the coast of Japan is currently under consideration, and environmental baseline studies of the area are required to understand possible impacts. The aim of this study is to clarify population structures of dominant benthic megafaunal species near hydrothermal vent fields in the Okinawa Trough, using a population genetics approach. We examined dominant deep-sea scavenging species including eels, several amphipods, and a decapod and performed population genetic analyses based on the mitochondrial cytochrome c oxidase subunit I region. Several sites were sampled within Okinawa Trough to examine intra-population diversity while two other locations 1400-2400 km away were chosen for inter-population comparisons. For synaphobranchid eels Simenchelys parasitica and Synaphobranchus kaupii, our results showed significant intra-population diversity but no inter-population genetic differentiation, suggesting strong genetic connectivity and/or large population sizes. In addition, single nucleotide polymorphism analysis also confirmed strong genetic connectivity for Simenchelys parasitica. Among scavenging amphipods, we detected seven putative species using molecular phylogenetic analysis. We evaluated population structures of the most abundant species of amphipods and a decapod species (Nematocarcinus lanceopes). Our results provide basic information on the genetic population structures of benthic megafaunal species near hydrothermal vent fields, which can be used to select candidate species for future connectivity analysis with high-resolution genetic markers and aid understanding of the potential population impacts of environmental disturbances.}, } @article {pmid36750641, year = {2023}, author = {Kayastha, P and Stec, D and Sługocki, Ł and Gawlak, M and Mioduchowska, M and Kaczmarek, Ł}, title = {Integrative taxonomy reveals new, widely distributed tardigrade species of the genus Paramacrobiotus (Eutardigrada: Macrobiotidae).}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2196}, pmid = {36750641}, issn = {2045-2322}, mesh = {Animals ; *Tardigrada/genetics ; Phylogeny ; Mitochondria/genetics ; Microscopy, Electron, Scanning ; RNA, Ribosomal, 18S/genetics ; }, abstract = {In a moss sample collected in Ribeiro Frio, Madeira, Paramacrobiotus gadabouti sp. nov. was found and described using the integrative taxonomy approach. The new species is described based on morphological and morphometric data from both phase-contrast light microscopy (PCM), as well as scanning electron microscopy (SEM). Moreover, four DNA markers, three nuclear (18S rRNA, 28S rRNA, ITS-2) and one mitochondrial (COI) markers, were used to elucidate the phylogenetic position of the new species within the family Macrobiotidae. The new species has a microplacoid that placed it within Parmacrobiotus richtersi group and exhibit richtersi-type eggs having processes terminated with cap-like structures. Paramacrobiotus gadabouti sp. nov. is most similar to Pam. alekseevi, Pam. filipi and Pam. garynahi, but differs from them mainly in details of egg morphology and morphometrics. Unlike other species from this group, which were confirmed as bisexual and showed limited distribution, Paramacrobiotus gadabouti sp. nov. is yet another parthenogenetic species with a wide distribution, demonstrating that at least some tardigrades confirm to the hypothesis of 'everything is everywhere'.}, } @article {pmid36746982, year = {2023}, author = {de Jong, MJ and Niamir, A and Wolf, M and Kitchener, AC and Lecomte, N and Seryodkin, IV and Fain, SR and Hagen, SB and Saarma, U and Janke, A}, title = {Range-wide whole-genome resequencing of the brown bear reveals drivers of intraspecies divergence.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {153}, pmid = {36746982}, issn = {2399-3642}, mesh = {Animals ; Male ; *Ursidae/genetics ; DNA, Mitochondrial/genetics ; Phylogeography ; Population Dynamics ; Mitochondria/genetics ; }, abstract = {Population-genomic studies can shed new light on the effect of past demographic processes on contemporary population structure. We reassessed phylogeographical patterns of a classic model species of postglacial recolonisation, the brown bear (Ursus arctos), using a range-wide resequencing dataset of 128 nuclear genomes. In sharp contrast to the erratic geographical distribution of mtDNA and Y-chromosomal haplotypes, autosomal and X-chromosomal multi-locus datasets indicate that brown bear population structure is largely explained by recent population connectivity. Multispecies coalescent based analyses reveal cases where mtDNA haplotype sharing between distant populations, such as between Iberian and southern Scandinavian bears, likely results from incomplete lineage sorting, not from ancestral population structure (i.e., postglacial recolonisation). However, we also argue, using forward-in-time simulations, that gene flow and recombination can rapidly erase genomic evidence of former population structure (such as an ancestral population in Beringia), while this signal is retained by Y-chromosomal and mtDNA, albeit likely distorted. We further suggest that if gene flow is male-mediated, the information loss proceeds faster in autosomes than in X chromosomes. Our findings emphasise that contemporary autosomal genetic structure may reflect recent population dynamics rather than postglacial recolonisation routes, which could contribute to mtDNA and Y-chromosomal discordances.}, } @article {pmid36748090, year = {2023}, author = {Zhang, Y and Li, W and Bian, Y and Li, Y and Cong, L}, title = {Multifaceted roles of aerobic glycolysis and oxidative phosphorylation in hepatocellular carcinoma.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e14797}, pmid = {36748090}, issn = {2167-8359}, abstract = {Liver cancer is a common malignancy with high morbidity and mortality rates. Changes in liver metabolism are key factors in the development of primary hepatic carcinoma, and mitochondrial dysfunction is closely related to the occurrence and development of tumours. Accordingly, the study of the metabolic mechanism of mitochondria in primary hepatic carcinomas has gained increasing attention. A growing body of research suggests that defects in mitochondrial respiration are not generally responsible for aerobic glycolysis, nor are they typically selected during tumour evolution. Conversely, the dysfunction of mitochondrial oxidative phosphorylation (OXPHOS) may promote the proliferation, metastasis, and invasion of primary hepatic carcinoma. This review presents the current paradigm of the roles of aerobic glycolysis and OXPHOS in the occurrence and development of hepatocellular carcinoma (HCC). Mitochondrial OXPHOS and cytoplasmic glycolysis cooperate to maintain the energy balance in HCC cells. Our study provides evidence for the targeting of mitochondrial metabolism as a potential therapy for HCC.}, } @article {pmid36747727, year = {2023}, author = {Espino-Sanchez, TJ and Wienkers, H and Marvin, RG and Nalder, SA and Garc A-Guerrero, AE and VanNatta, PE and Jami-Alahmadi, Y and Blackwell, AM and Whitby, FG and Wohlschlegel, JA and Kieber-Emmons, MT and Hill, CP and Sigala, PA}, title = {Direct Tests of Cytochrome Function in the Electron Transport Chain of Malaria Parasites.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.01.23.525242}, pmid = {36747727}, abstract = {UNLABELLED: The mitochondrial electron transport chain (ETC) of Plasmodium malaria parasites is a major antimalarial drug target, but critical cytochrome functions remain unstudied and enigmatic. Parasites express two distinct cyt c homologs (c and c -2) with unusually sparse sequence identity and uncertain fitness contributions. P. falciparum cyt c -2 is the most divergent eukaryotic cyt c homolog currently known and has sequence features predicted to be incompatible with canonical ETC function. We tagged both cyt c homologs and the related cyt c 1 for inducible knockdown. Translational repression of cyt c and cyt c 1 was lethal to parasites, which died from ETC dysfunction and impaired ubiquinone recycling. In contrast, cyt c -2 knockdown or knock-out had little impact on blood-stage growth, indicating that parasites rely fully on the more conserved cyt c for ETC function. Biochemical and structural studies revealed that both cyt c and c -2 are hemylated by holocytochrome c synthase, but UV-vis absorbance and EPR spectra strongly suggest that cyt c -2 has an unusually open active site in which heme is stably coordinated by only a single axial amino-acid ligand and can bind exogenous small molecules. These studies provide a direct dissection of cytochrome functions in the ETC of malaria parasites and identify a highly divergent Plasmodium cytochrome c with molecular adaptations that defy a conserved role in eukaryotic evolution.

SIGNIFICANCE STATEMENT: Mitochondria are critical organelles in eukaryotic cells that drive oxidative metabolism. The mitochondrion of Plasmodium malaria parasites is a major drug target that has many differences from human cells and remains poorly studied. One key difference from humans is that malaria parasites express two cytochrome c proteins that differ significantly from each other and play untested and uncertain roles in the mitochondrial electron transport chain (ETC). Our study revealed that one cyt c is essential for ETC function and parasite viability while the second, more divergent protein has unusual structural and biochemical properties and is not required for growth of blood-stage parasites. This work elucidates key biochemical properties and evolutionary differences in the mitochondrial ETC of malaria parasites.}, } @article {pmid36732530, year = {2023}, author = {Silva, MC and Catry, P and Bried, J and Kawakami, K and Flint, E and Granadeiro, JP}, title = {Contrasting patterns of population structure of Bulwer's petrel (Bulweria bulwerii) between oceans revealed by statistical phylogeography.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {1939}, pmid = {36732530}, issn = {2045-2322}, mesh = {Animals ; Phylogeography ; Oceans and Seas ; *Birds/genetics ; Pacific Ocean ; *Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Phylogeny ; Genetic Variation ; }, abstract = {The patterns of population divergence of mid-latitude marine birds are impacted by only a few biogeographic barriers to dispersal and the effect of intrinsic factors, such as fidelity to natal colonies or wintering grounds, may become more conspicuous. Here we describe, for the first time, the phylogeographic patterns and historical demography of Bulwer's petrel Bulweria bulwerii and provide new insights regarding the drivers of species diversification in the marine environment. We sampled Bulwer's petrels from the main breeding colonies and used a statistical phylogeography approach based on surveying nuclear and mitochondrial loci (~ 9100 bp) to study its mechanisms of global diversification. We uncovered three highly differentiated groups including the Western Pacific, the Central Pacific and the Atlantic. The older divergence occurred within the Pacific Ocean, ca. 850,000 ya, and since then the W Pacific group has been evolving in isolation. Conversely, divergence between the Central Pacific and Atlantic populations occurred within the last 200,000 years. While the Isthmus of Panama is important in restricting gene flow between oceans in Bulwer's petrels, the deepest phylogeographic break is within the Pacific Ocean, where oceanographic barriers are key in driving and maintaining the remarkable structure found in this highly mobile seabird. This is in contrast with the Atlantic, where no structure was detected. Further data will provide insights regarding the extent of lineage divergence of Bulwer's petrels in the Western Pacific.}, } @article {pmid36331499, year = {2023}, author = {Lestari, SM and Khatun, MF and Acharya, R and Sharma, SR and Shrestha, YK and Jahan, SMH and Aye, TT and Lynn, OM and Win, NKK and Hoat, TX and Thi Dao, H and Tsai, CW and Lee, J and Hwang, HS and Kil, EJ and Lee, S and Kim, SM and Lee, KY}, title = {Genetic diversity of cryptic species of Bemisia tabaci in Asia.}, journal = {Archives of insect biochemistry and physiology}, volume = {112}, number = {2}, pages = {e21981}, doi = {10.1002/arch.21981}, pmid = {36331499}, issn = {1520-6327}, mesh = {Animals ; Phylogeny ; Asia ; China ; *Mitochondria ; *Hemiptera/genetics ; Genetic Variation ; }, abstract = {Bemisia tabaci is a species complex consisting of various genetically different cryptic species worldwide. To understand the genetic characteristics and geographic distribution of cryptic species of B. tabaci in Asia, we conducted an extensive collection of B. tabaci samples in ten Asian countries (Bangladesh, Indonesia, Japan, Korea, Myanmar, Nepal, Philippines, Singapore, Taiwan, and Vietnam) from 2013 to 2020 and determined 56 different partial sequences of mitochondrial cytochrome oxidase subunit I (COI) DNA. In addition, information on 129 COI sequences of B. tabaci identified from 16 Asian countries was downloaded from the GenBank database. Among the total 185 COI sequences of B. tabaci, the sequence variation reached to 19.68%. In addition, there were 31 cryptic species updated from 16 countries in Asia, that is, Asia I, Asia I India, Asia II (1-13), Asia III, Asia IV, Asia V, China 1-6, MEAM (1, 2, K), MED, Australia/Indonesia, Japan (1 and 2). Further, MED cryptic species consisted of 2 clades, Q1 and Q2. This study provides updated information to understand the genetic variation and geographic diversity of B. tabaci in Asia.}, } @article {pmid36739946, year = {2023}, author = {Schmitz, JM and Wolters, JF and Murray, NH and Guerra, RM and Bingman, CA and Hittinger, CT and Pagliarini, DJ}, title = {Aim18p and Aim46p are chalcone isomerase (CHI)-domain-containing mitochondrial hemoproteins in Saccharomyces cerevisiae.}, journal = {The Journal of biological chemistry}, volume = {}, number = {}, pages = {102981}, doi = {10.1016/j.jbc.2023.102981}, pmid = {36739946}, issn = {1083-351X}, abstract = {Chalcone isomerases (CHIs) have well-established roles in the biosynthesis of plant flavonoid metabolites. Saccharomyces cerevisiae possesses two predicted CHI-like proteins, Aim18p (encoded by YHR198C) and Aim46p (YHR199C), but it lacks other enzymes of the flavonoid pathway, suggesting that Aim18p and Aim46p employ the CHI fold for distinct purposes. Here, we demonstrate using proteinase K protection assays, sodium carbonate extractions, and crystallography that Aim18p and Aim46p reside on the mitochondrial inner membrane and adopt CHI folds, but they lack select active site residues and possess an extra fungal-specific loop. Consistent with these differences, Aim18p and Aim46p lack chalcone isomerase activity and also the fatty acid-binding capabilities of other CHI-like proteins, but instead bind heme. We further show that diverse fungal homologs also bind heme and that Aim18p and Aim46p possess structural homology to a bacterial hemoprotein. Collectively, our work reveals a distinct function and cellular localization for two CHI-like proteins, introduces a new variation of a hemoprotein fold, and suggests that ancestral CHI-like proteins were hemoproteins.}, } @article {pmid36739562, year = {2023}, author = {Fang, JM and Basu, S and Phu, J and Nieh, MP and LoTurco, JJ}, title = {Cellular Localization, Aggregation, and Cytotoxicity of Bicelle-Quantum Dot Nanocomposites.}, journal = {ACS applied bio materials}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsabm.2c00827}, pmid = {36739562}, issn = {2576-6422}, abstract = {Bicelles are discoidal lipid nanoparticles (LNPs) in which the planar bilayer and curved rim are, respectively, composed of long- and short-chain lipids. Bicellar LNPs have a hydrophobic core, allowing hydrophobic molecules and large molecular complexes such as quantum dots (QDs) to be encapsulated. In this study, CdSe/ZnS QDs were encapsulated in bicelles made of dipalmitoyl phosphatidylcholine, dihexanoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol, and distearoyl phosphatidylethanolamine conjugated with polyethylene glycerol amine 2000 to form a well-defined bicelle-QD nanocomplex (known as NANO[2]-QD or bicelle-QD). The bicelle-QD was then incubated with Hek293t cells and HeLa cells for different periods of time to determine changes in their cellular localization. Bicelle-QDs readily penetrated Hek293t cell membranes within 15 min of incubation, localized to the cytoplasm, and associated with mitochondria and intracellular vesicles. After 1 h, the bicelle-QDs enter the cell nucleus. Large aggregates form throughout the cell after 2 h and QDs are nearly absent from the nucleus by 4 h. Previous reports have demonstrated that CdSe/ZnS QDs can be toxic to cells, and we have found that encapsulating QDs in bicelles can attenuate but did not eliminate cytotoxicity. The present research outcome demonstrates the time-resolved pathway of bicelle-encapsulated QDs in Hek293t cells, morphological evolution in cells over time, and cytotoxicity of the bicelle-QDs, providing important insight into the potential application of the nanocomplex for cellular imaging.}, } @article {pmid36738170, year = {2023}, author = {Rogers, RL and Grizzard, SL and Garner, JT}, title = {Strong, recent selective sweeps reshape genetic diversity in freshwater bivalve Megalonaias nervosa.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msad024}, pmid = {36738170}, issn = {1537-1719}, abstract = {Freshwater Unionid bivalves have recently faced ecological upheaval through pollution, barriers to dispersal, harvesting, and changes in _sh-host prevalence. Currently, over 70% of species in North America are threatened, endangered or extinct. To characterize the genetic response to recent selective pressures, we collected population genetic data for one successful bivalve species, Megalonaias nervosa. We identify megabase sized regions that are nearly monomorphic across the population, signals of strong, recent selection reshaping diversity across 73Mb total. These signatures of selection are greater than is commonly seen in population genetic models. We observe 102 duplicate genes with high dN/dS on terminal branches among regions with sweeps, suggesting that gene duplication is a causative mechanism of recent adaptation in M. nervosa. Genes in sweeps reect functional classes important for Unionid survival, including anticoagulation genes important for _sh host parasitization, detox genes, mitochondria management, and shell formation. We identify sweeps in regions with no known functional impacts, suggesting mechanisms of adaptation that deserve greater attention in future work on species survival. In contrast, polymorphic transposable elements appear to be detrimental and underrepresented among regions with sweeps. TE site frequency spectra are skewed toward singleton variants, and TEs among regions with sweeps are present at low frequency. Our work suggests that duplicate genes are an essential source of genetic novelty that has helped this successful species succeed in environments where others have struggled. These results suggest that gene duplications deserve greater attention in non-model population genomics, especially in species that have recently faced sudden environmental challenges.}, } @article {pmid36737563, year = {2023}, author = {Rottenberg, H}, title = {The evolution of the human mitochondrial bc1 complex- adaptation for reduced rate of superoxide production?.}, journal = {Journal of bioenergetics and biomembranes}, volume = {}, number = {}, pages = {}, pmid = {36737563}, issn = {1573-6881}, abstract = {The mitochondrial bc1 complex is a major source of mitochondrial superoxide. While bc1-generated superoxide plays a beneficial signaling role, excess production of superoxide lead to aging and degenerative diseases. The catalytic core of bc1 comprises three peptides -cytochrome b, Fe-S protein, and cytochrome c1. All three core peptides exhibit accelerated evolution in anthropoid primates. It has been suggested that the evolution of cytochrome b in anthropoids was driven by a pressure to reduce the production of superoxide. In humans, the bc1 core peptides exhibit anthropoid-specific substitutions that are clustered near functionally critical sites that may affect the production of superoxide. Here we compare the high-resolution structures of bovine, mouse, sheep and human bc1 to identify structural changes that are associated with human-specific substitutions. Several cytochrome b substitutions in humans alter its interactions with other subunits. Most significantly, there is a cluster of seven substitutions, in cytochrome b, the Fe-S protein, and cytochrome c1 that affect the interactions between these proteins at the tether arm of the Fe-S protein and may alter the rate of ubiquinone oxidation and the rate of superoxide production. Another cluster of substitutions near heme bH and the ubiquinone reduction site, Qi, may affect the rate of ubiquinone reduction and thus alter the rate of superoxide production. These results are compatible with the hypothesis that cytochrome b in humans (and other anthropoid primates) evolve to reduce the rate of production of superoxide thus enabling the exceptional longevity and exceptional cognitive ability of humans.}, } @article {pmid36734850, year = {2023}, author = {Nord, A and Chamkha, I and Elmér, E}, title = {A whole blood approach improves speed and accuracy when measuring mitochondrial respiration in intact avian blood cells.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {37}, number = {3}, pages = {e22766}, doi = {10.1096/fj.202201749R}, pmid = {36734850}, issn = {1530-6860}, abstract = {Understanding mitochondrial biology and pathology is key to understanding the evolution of animal form and function. However, mitochondrial measurement often involves invasive, or even terminal, sampling, which can be difficult to reconcile in wild models or longitudinal studies. Non-mammal vertebrates contain mitochondria in their red blood cells, which can be exploited for minimally invasive mitochondrial measurement. Several recent bird studies have measured mitochondrial function using isolated blood cells. Isolation adds time in the laboratory and might be associated with physiological complications. We developed and validated a protocol to measure mitochondrial respiration in bird whole blood. Endogenous respiration was comparable between isolated blood cells and whole blood. However, respiration towards oxidative phosphorylation was higher in whole blood, and whole blood mitochondria were better coupled and had higher maximum working capacity. Whole blood measurement was also more reproducible than measurement on isolated cells for all traits considered. Measurements were feasible over a 10-fold range of sample volumes, although both small and large volumes were associated with changes to respiratory traits. The protocol was compatible with long-term storage: after 24 h at 5°C without agitation, all respiration traits but maximum working capacity remained unchanged, the latter decreasing by 14%. Our study suggests that whole blood measurement provides faster, more reproducible, and more biologically and physiologically relevant (mitochondrial integrity) assessment of mitochondrial respiration. We recommend future studies to take a whole blood approach unless specific circumstances require the use of isolated blood cells.}, } @article {pmid36726084, year = {2023}, author = {Li, Y and Gu, M and Liu, X and Lin, J and Jiang, H and Song, H and Xiao, X and Zhou, W}, title = {Sequencing and analysis of the complete mitochondrial genomes of Toona sinensis and Toona ciliata reveal evolutionary features of Toona.}, journal = {BMC genomics}, volume = {24}, number = {1}, pages = {58}, pmid = {36726084}, issn = {1471-2164}, mesh = {Toona/genetics ; Phylogeny ; *Genome, Mitochondrial ; Plant Breeding ; *Meliaceae/genetics ; }, abstract = {BACKGROUND: Toona is a critical genus in the Meliaceae, and the plants of this group are an asset for both restorative and restorative purposes, the most flexible of which are Toona sinensis and Toona ciliata. To concentrate on the advancement of mitochondrial(Mt) genome variety in T.sinensis and T.ciliata, the Mt genomes of the two species were sequenced in high throughput independently, after de novo assembly and annotation to construct a Mt genome map for comparison in genome structure. Find their repetitive sequences and analyze them in comparison with the chloroplast genome, along with Maximum-likelihood(ML) phylogenetic analysis with 16 other relatives.

RESULTS: (1) T. sinensis and T.ciliata are both circular structures with lengths of 683482 bp and 68300 bp, respectively. They share a high degree of similarity in encoding genes and have AT preferences. All of them have the largest Phe concentration and are the most frequently used codons. (2) Both of their Mt genome are highly preserved in terms of structural and functional genes, while the main variability is reflected in the length of tRNA, the number of genes, and the value of RSCU. (3) T. siniensis and T. ciliata were detected to have 94 and 87 SSRs, respectively, of which mononucleotides accounted for the absolute proportion. Besides, the vast majority of their SSRs were found to be poly-A or poly-T. (4)10 and 11 migrating fragments were identified in the comparison with the chloroplast genome, respectively. (5) In the ML evolutionary tree, T.sinensis and T.ciliata clustered individually into a small branch with 100% support, reflecting two species of Toona are very similarly related to each other.

CONCLUSIONS: This research provides a basis for the exploitation of T.sinensis and T.ciliata in terms of medicinal, edible, and timber resources to avoid confusion; at the same time, it can explore the evolutionary relationship between the Toona and related species, which does not only have an important practical value, but also provides a theoretical basis for future hybrid breeding of forest trees, molecular markers, and evolutionary aspects of plants, which has great scientific significance.}, } @article {pmid36722300, year = {2023}, author = {Russo, MT and Santin, A and Zuccarotto, A and Leone, S and Palumbo, A and Ferrante, MI and Castellano, I}, title = {The first genetic engineered system for ovothiol biosynthesis in diatoms reveals a mitochondrial localization for the sulfoxide synthase OvoA.}, journal = {Open biology}, volume = {13}, number = {2}, pages = {220309}, doi = {10.1098/rsob.220309}, pmid = {36722300}, issn = {2046-2441}, abstract = {Diatoms represent one of the most abundant groups of microalgae in the ocean and are responsible for approximately 20% of photosynthetically fixed CO2 on Earth. Due to their complex evolutionary history and ability to adapt to different environments, diatoms are endowed with striking molecular biodiversity and unique metabolic activities. Their high growth rate and the possibility to optimize their biomass make them very promising 'biofactories' for biotechnological applications. Among bioactive compounds, diatoms can produce ovothiols, histidine-derivatives, endowed with unique antioxidant and anti-inflammatory properties, and occurring in many marine invertebrates, bacteria and pathogenic protozoa. However, the functional role of ovothiols biosynthesis in organisms remains almost unexplored. In this work, we have characterized the thiol fraction of Phaeodactylum tricornutum, providing the first evidence of the presence of ovothiol B in pennate diatoms. We have used P. tricornutum to overexpress the 5-histidylcysteine sulfoxide synthase ovoA, the gene encoding the key enzyme involved in ovothiol biosynthesis and we have discovered that OvoA localizes in the mitochondria, a finding that uncovers new concepts in cellular redox biochemistry. We have also obtained engineered biolistic clones that can produce higher amount of ovothiol B compared to wild-type cells, suggesting a new strategy for the eco-sustainable production of these molecules.}, } @article {pmid36717086, year = {2023}, author = {Nishita, Y and Amaike, Y and Spassov, N and Hristova, L and Kostov, D and Vladova, D and Peeva, S and Raichev, E and Vlaeva, R and Masuda, R}, title = {Diversity of mitochondrial D-loop haplotypes from ancient Thracian horses in Bulgaria.}, journal = {Animal science journal = Nihon chikusan Gakkaiho}, volume = {94}, number = {1}, pages = {e13810}, doi = {10.1111/asj.13810}, pmid = {36717086}, issn = {1740-0929}, mesh = {Horses/genetics ; Animals ; Bulgaria ; Haplotypes/genetics ; Phylogeny ; *Mitochondria/genetics ; *DNA, Mitochondrial/genetics ; Genetic Variation ; }, abstract = {The domestication of the horse began possibly more than 5000 years ago in the western part of the Eurasian steppe, and according to the leading hypothesis, horses first spread from the Steppe toward the region of the Thracian culture, starting in the second half of the 2nd millennium BCE and flourished from the fifth to first centuries BCE, mainly located in present-day Bulgaria. We analyzed 17 horse bone remains excavated from Thracian archaeological sites (fourth to first centuries BCE) in Bulgaria and successfully identified 17 sequences representing 14 different haplotypes of the mitochondrial D-loop. Compared with the mtDNA haplotypes of modern horses around the world, ancient Thracian horses in Bulgaria are thought to be more closely related to modern horses of Southern Europe and less related to those of Central Asia. In addition, the haplotypes we obtained represented 11 previously reported modern horse mtDNA haplogroups: A, B, D, E, G, H, I, L, N, P, and Q. All the haplogroups contain modern and regionally predominant haplotypes occurring in Europe, the Middle East, and Central Asia. Our results indicate that Thracian horses in Bulgaria have had relatively high genetic diversity and are closely related to modern horse breeds.}, } @article {pmid36717448, year = {2022}, author = {Shilovsky, GA and Putyatina, TS and Markov, AV}, title = {Evolution of Longevity as a Species-Specific Trait in Mammals.}, journal = {Biochemistry. Biokhimiia}, volume = {87}, number = {12}, pages = {1579-1599}, doi = {10.1134/S0006297922120148}, pmid = {36717448}, issn = {1608-3040}, abstract = {From the evolutionary point of view, the priority problem for an individual is not longevity, but adaptation to the environment associated with the need for survival, food supply, and reproduction. We see two main vectors in the evolution of mammals. One is a short lifespan and numerous offspring ensuring reproductive success (r-strategy). The other one is development of valuable skills in order compete successfully (K-strategy). Species with the K-strategy should develop and enhance specific systems (anti-aging programs) aimed at increasing the reliability and adaptability, including lifespan. These systems are signaling cascades that provide cell repair and antioxidant defense. Hence, any arbitrarily selected long-living species should be characterized by manifestation to a different extent of the longevity-favoring traits (e.g., body size, brain development, sociality, activity of body repair and antioxidant defense systems, resistance to xenobiotics and tumor formation, presence of neotenic traits). Hereafter, we will call a set of such traits as the gerontological success of a species. Longevity is not equivalent to the evolutionary or reproductive success. This difference between these phenomena reaches its peak in mammals due to the development of endothermy and cephalization associated with the cerebral cortex expansion, which leads to the upregulated production of oxidative radicals by the mitochondria (and, consequently, accelerated aging), increase in the number of non-dividing differentiated cells, accumulation of the age-related damage in these cells, and development of neurodegenerative diseases. The article presents mathematical indicators used to assess the predisposition to longevity in different species (including the standard mortality rate and basal metabolic rate, as well as their derivatives). The properties of the evolution of mammals (including the differences between modern mammals and their ancestral forms) are also discussed.}, } @article {pmid36702320, year = {2023}, author = {Buonvicino, D and Ranieri, G and Guasti, D and Pistolesi, A and La Rocca, AI and Rapizzi, E and Chiarugi, A}, title = {Early derangement of axonal mitochondria occurs in a mouse model of progressive but not relapsing-remitting multiple sclerosis.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {106015}, doi = {10.1016/j.nbd.2023.106015}, pmid = {36702320}, issn = {1095-953X}, abstract = {INTRODUCTION: Derangement of axonal mitochondrial bioenergetics occurs during progressive multiple sclerosis (PMS). However, whether this is a delayed epiphenomenon or an early causative event of disease progression waits to be understood. Answering this question might further our knowledge of mechanisms underlying neurobiology of PMS and related therapy.

METHODS: MOG35-55-immunized NOD and PLP139-151-immunized SJL female mice were adopted as models of progressive or relapsing-remitting experimental autoimmune encephalomyelitis (EAE), respectively. Multiple parameters of mitochondrial homeostasis were analyzed in the mouse spinal cord during the early asymptomatic stage, also evaluating the effects of scavenging mitochondrial reactive oxygen species with Mito-TEMPO.

RESULTS: Almost identical lumbar spinal cord immune infiltrates consisting of Th1 cells and neutrophils without B and Th17 lymphocytes occurred early upon immunization in both mouse strains. Still, only NOD mice showed axon-restricted dysregulation of mitochondrial homeostasis, with reduced mtDNA contents and increased cristae area. Increased expression of mitochondrial respiratory complex subunits Nd2, Cox1, Atp5d, Sdha also exclusively occurred in lumbar spinal cord of NOD and not SJL mice. Accordingly, in this region genes regulating mitochondrial morphology (Opa1, Mfn1, Mfn2 and Atp5j2) and mitochondriogenesis (Pgc1α, Foxo, Hif-1α and Nrf2) were induced early upon immunization. A reduced extent of mitochondrial derangement occurred in the thoracic spinal cord. Notably, the mitochondrial radical scavenger Mito-TEMPO reduced H2O2 content and prevented both mtDNA depletion and cristae remodeling, having no effects on dysregulation of mitochondrial transcriptome.

DISCUSSION: We provide here the first evidence that axonal-restricted derangement of mitochondrial homeostasis already occurs during the asymptomatic state exclusively in a mouse model of PMS. Data further our understanding of mechanisms related to EAE progression, and point to very early axonal mitochondrial dysfunction as central to the neuropathogenesis of MS evolution.}, } @article {pmid36672951, year = {2023}, author = {Zhang, T and Wang, Y and Song, H}, title = {The Complete Mitochondrial Genome and Gene Arrangement of the Enigmatic Scaphopod Pictodentalium vernedei.}, journal = {Genes}, volume = {14}, number = {1}, pages = {}, pmid = {36672951}, issn = {2073-4425}, mesh = {Animals ; *Genome, Mitochondrial ; Phylogeny ; Gene Order ; Mollusca/genetics ; Mitochondria/genetics ; }, abstract = {The enigmatic scaphopods, or tusk shells, are a small and rare group of molluscs whose phylogenomic position among the Conchifera is undetermined, and the taxonomy within this class also needs revision. Such work is hindered by there only being a very few mitochondrial genomes in this group that are currently available. Here, we present the assembly and annotation of the complete mitochondrial genome from Dentaliida Pictodentalium vernedei, whose mitochondrial genome is 14,519 bp in size, containing 13 protein-coding genes, 22 tRNA genes and two rRNA genes. The nucleotide composition was skewed toward A-T, with a 71.91% proportion of AT content. Due to the mitogenome-based phylogenetic analysis, we defined P. vernedei as a sister to Graptacme eborea in Dentaliida. Although a few re-arrangements occurred, the mitochondrial gene order showed deep conservation within Dentaliida. Yet, such a gene order in Dentaliida largely diverges from Gadilida and other molluscan classes, suggesting that scaphopods have the highest degree of mitogenome arrangement compared to other molluscs.}, } @article {pmid36446749, year = {2023}, author = {Li, SP and Jiang, H and Liu, ZB and Yu, WJ and Cai, XS and Liu, C and Xie, WY and Quan, FS and Gao, W and Kim, NH and Yuan, B and Chen, CZ and Zhang, JB}, title = {TBX2 affects proliferation, apoptosis and cholesterol generation by regulating mitochondrial function and autophagy in bovine cumulus cell.}, journal = {Veterinary medicine and science}, volume = {9}, number = {1}, pages = {326-335}, doi = {10.1002/vms3.1009}, pmid = {36446749}, issn = {2053-1095}, mesh = {Female ; Animals ; Cattle ; *Cumulus Cells/metabolism ; Cell Proliferation ; *Autophagy ; Apoptosis/genetics ; Mitochondria ; Cholesterol/metabolism/pharmacology ; Adenosine Triphosphate/metabolism/pharmacology ; }, abstract = {BACKGROUND: T-box transcription factor 2 (TBX2) is a member of T-box gene family whose members are highly conserved in evolution and encoding genes and are involved in the regulation of developmental processes. The encoding genes play an important role in growth and development. Although TBX2 has been widely studied in cancer cell growth and development, its biological functions in bovine cumulus cells remain unclear.

OBJECTIVES: This study aimed to investigate the regulatory effects of TBX2 in bovine cumulus cells.

METHODS: TBX2 gene was knockdown with siRNA to clarify the function in cellular physiological processes. Cell proliferation and cycle changes were determined by xCELLigence cell function analyzer and flow cytometry. Mitochondrial membrane potential and autophagy were detected by fluorescent dye staining and immunofluorescence techniques. Western blot and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression changes of proliferation and autophagy-related proteins. Aadenosine triphosphate (ATP) production, glucose metabolism, and cholesterol synthesis of cumulus cells were measured by optical density and chemiluminescence analysis.

RESULTS: After inhibition of TBX2, the cell cycle was disrupted. The levels of apoptosis, ratio of light chain 3 beta II/I, and reactive oxygen species were increased. The proliferation, expansion ability, ATP production, and the amount of cholesterol secreted by cumulus cells were significantly decreased.

CONCLUSIONS: TBX2 plays important roles in regulating the cells' proliferation, expansion, apoptosis, and autophagy; maintaining the mitochondrial function and cholesterol generation of bovine cumulus cells.}, } @article {pmid36336814, year = {2023}, author = {Vilaça, ST and Maroso, F and Lara, P and de Thoisy, B and Chevallier, D and Arantes, LS and Santos, FR and Bertorelle, G and Mazzoni, CJ}, title = {Evidence of backcross inviability and mitochondrial DNA paternal leakage in sea turtle hybrids.}, journal = {Molecular ecology}, volume = {32}, number = {3}, pages = {628-643}, doi = {10.1111/mec.16773}, pmid = {36336814}, issn = {1365-294X}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Turtles/genetics ; Mitochondria/genetics ; Biological Evolution ; Polymerase Chain Reaction ; }, abstract = {Hybridization is known to be part of many species' evolutionary history. Sea turtles have a fascinating hybridization system in which species separated by as much as 43 million years are still capable of hybridizing. Indeed, the largest nesting populations in Brazil of loggerheads (Caretta caretta) and hawksbills (Eretmochelys imbricata) have a high incidence of hybrids between these two species. A third species, olive ridleys (Lepidochelys olivacea), is also known to hybridize although at a smaller scale. Here, we used restriction site-associated DNA sequencing (RAD-Seq) markers, mitogenomes, and satellite-telemetry to investigate the patterns of hybridization and introgression in the Brazilian sea turtle population and their relationship with the migratory behaviours between feeding and nesting aggregations. We also explicitly test if the mixing of two divergent genomes in sea turtle hybrids causes mitochondrial paternal leakage. We developed a new species-specific PCR-assay capable of detecting mitochondrial DNA (mtDNA) inheritance from both parental species and performed ultra-deep sequencing to estimate the abundance of each mtDNA type. Our results show that all adult hybrids are first generation (F1) and most display a loggerhead migratory behaviour. We detected paternal leakage in F1 hybrids and different proportions of mitochondria from maternal and paternal species. Although previous studies showed no significant fitness decrease in hatchlings, our results support genetically-related hybrid breakdown possibly caused by cytonuclear incompatibility. Further research on hybrids from other populations in addition to Brazil and between different species will show if backcross inviability and mitochondrial paternal leakage is observed across sea turtle species.}, } @article {pmid36644898, year = {2023}, author = {He, W and Xiang, K and Chen, C and Wang, J and Wu, Z}, title = {Master graph: an essential integrated assembly model for the plant mitogenome based on a graph-based framework.}, journal = {Briefings in bioinformatics}, volume = {24}, number = {1}, pages = {}, doi = {10.1093/bib/bbac522}, pmid = {36644898}, issn = {1477-4054}, mesh = {Animals ; *Genome, Mitochondrial ; DNA, Mitochondrial/genetics ; Biological Evolution ; Mitochondria/genetics ; Plants/genetics ; Phylogeny ; }, abstract = {Unlike the typical single circular structure of most animal mitochondrial genomes (mitogenome), the drastic structural variation of plant mitogenomes is a result of a mixture of molecules of various sizes and structures. Obtaining the full panoramic plant mitogenome is still considered a roadblock in evolutionary biology. In this study, we developed a graph-based sequence assembly toolkit (GSAT) to construct the pan-structural landscape of plant mitogenome with high-quality mitochondrial master graphs (MMGs) for model species including rice (Oryza sativa) and thale cress (Arabidopsis thaliana). The rice and thale cress MMGs have total lengths of 346 562 and 358 041 bp, including 9 and 6 contigs and 12 and 8 links, respectively, and could be further divided into 6 and 3 minimum master circles and 4 and 2 minimum secondary circles separately. The nuclear mitochondrial DNA segments (NUMTs) in thale cress strongly affected the frequency evaluation of the homologous structures in the mitogenome, while the effects of NUMTs in rice were relatively weak. The mitochondrial plastid DNA segments (MTPTs) in both species had no effects on the assessment of the MMGs. All potential recombinant structures were evaluated, and the findings revealed that all, except for nuclear-homologous structures, MMG structures are present at a much higher frequency than non-MMG structures are. Investigations of potential circular and linear molecules further supported multiple dominant structures in the mitogenomes and could be completely summarized in the MMG. Our study provided an efficient and accurate model for assembling and applying graph-based plant mitogenomes to assess their pan-structural variations.}, } @article {pmid36563715, year = {2023}, author = {Shukla, P and Mukherjee, S and Patil, A and Joshi, B}, title = {Molecular characterization of variants in mitochondrial DNA encoded genes using next generation sequencing analysis and mitochondrial dysfunction in women with PCOS.}, journal = {Gene}, volume = {855}, number = {}, pages = {147126}, doi = {10.1016/j.gene.2022.147126}, pmid = {36563715}, issn = {1879-0038}, mesh = {Humans ; Female ; DNA, Mitochondrial/genetics ; High-Throughput Nucleotide Sequencing/methods ; *Polycystic Ovary Syndrome/genetics ; Mitochondria/genetics ; RNA, Transfer ; *Genome, Mitochondrial ; }, abstract = {Emerging studies indicates mitochondrial dysfunction and involvement of mitochondrial DNA (mtDNA) variants in the pathogenesis of polycystic ovary syndrome (PCOS). Cumulative effect of mtDNA rare variants are now gaining considerable interest apart from common variants in the pathogenesis of complex diseases. Rare variants may modify the effect of polymorphism or in combination with the common variants may affect the risk of disease. With the evolution of high throughput sequencing techniques, which can be utilized to identify common as well as rare variants along with heteroplasmy levels, comprehensive characterization of the mtDNA variants is possible. Till date, few studies reported common mtDNA variants using traditional sequencing techniques but rare variants in mtDNA encoding genes remain unexplored in women with PCOS. These mtDNA variants may be responsible for mitochondrial dysfunction and may contribute in PCOS pathogenesis. In this study we determined mtDNA copy number, a biomarker of mitochondrial dysfunction and first time analysed variants in mtDNA encoded genes in women with PCOS using mitochondrial Next Generation sequencing (NGS) approach and compared allele frequency from mitochondrial 1000 genome dataset. Variant annotation and prioritization was done using highly automated pipeline, MToolBox that excludes reads mapped from nuclear mitochondrial DNA sequences (NumtS) to identify unique mtDNA reads. The present study identified significant reduction in mtDNA copy number in women with PCOS compared to non-PCOS women. A total of unique 214 prioritized common to rare variants were identified in mtDNA encoded genes, 183 variants in OXPHOS complexes, 14 variants in MT-tRNA and 17 variants in MT-rRNA genes that may be involved in mitochondrial dysfunction in PCOS. Numerous variants were heteroplasmic, pathogenic in nature and occurred in evolutionary conserved region. Heteroplasmic variants were more frequently occurred in MT-CO3 gene. Non-synonymous variants were more than synonymous variants and mainly occurred in OXPHOS complex I and IV. Few variants were found to be associated with diseases in MITOMAP database. The study provides a better understanding towards pathogenesis of PCOS from novel aspects focusing on mitochondrial genetic defects as underlying cause for contributing mitochondrial dysfunction in women with PCOS.}, } @article {pmid36671555, year = {2023}, author = {Righetto, I and Gasparotto, M and Casalino, L and Vacca, M and Filippini, F}, title = {Exogenous Players in Mitochondria-Related CNS Disorders: Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis.}, journal = {Biomolecules}, volume = {13}, number = {1}, pages = {}, doi = {10.3390/biom13010169}, pmid = {36671555}, issn = {2218-273X}, abstract = {Billions of years of co-evolution has made mitochondria central to the eukaryotic cell and organism life playing the role of cellular power plants, as indeed they are involved in most, if not all, important regulatory pathways. Neurological disorders depending on impaired mitochondrial function or homeostasis can be caused by the misregulation of "endogenous players", such as nuclear or cytoplasmic regulators, which have been treated elsewhere. In this review, we focus on how exogenous agents, i.e., viral pathogens, or unbalanced microbiota in the gut-brain axis can also endanger mitochondrial dynamics in the central nervous system (CNS). Neurotropic viruses such as Herpes, Rabies, West-Nile, and Polioviruses seem to hijack neuronal transport networks, commandeering the proteins that mitochondria typically use to move along neurites. However, several neurological complications are also associated to infections by pandemic viruses, such as Influenza A virus and SARS-CoV-2 coronavirus, representing a relevant risk associated to seasonal flu, coronavirus disease-19 (COVID-19) and "Long-COVID". Emerging evidence is depicting the gut microbiota as a source of signals, transmitted via sensory neurons innervating the gut, able to influence brain structure and function, including cognitive functions. Therefore, the direct connection between intestinal microbiota and mitochondrial functions might concur with the onset, progression, and severity of CNS diseases.}, } @article {pmid36670920, year = {2022}, author = {Cruz-Gregorio, A and Aranda-Rivera, AK and Aparicio-Trejo, OE and Medina-Campos, ON and Sciutto, E and Fragoso, G and Pedraza-Chaverri, J}, title = {GK-1 Induces Oxidative Stress, Mitochondrial Dysfunction, Decreased Membrane Potential, and Impaired Autophagy Flux in a Mouse Model of Breast Cancer.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/antiox12010056}, pmid = {36670920}, issn = {2076-3921}, abstract = {Breast cancer (BC) is the second most common cancer worldwide in women. During the last decades, the mortality due to breast cancer has progressively decreased due to early diagnosis and the emergence of more effective new treatments. However, human epidermal growth factor receptor 2 (HER2) and triple-negative breast cancer (TNBC) remain with poor prognoses. In our research group, we are proposing the GK-1 immunomodulatory peptide as a new alternative for immunotherapy of these aggressive tumors. GK-1 reduced the growth rate of established tumors and effectively reduced lung metastasis in the 4T1 experimental murine model of breast cancer. Herein, the effect of GK-1 on the redox state, mitochondrial metabolism, and autophagy of triple-negative tumors that can be linked to cancer evolution was studied. GK-1 decreased catalase activity, reduced glutathione (GSH) content and GSH/oxidized glutathione (GSSG) ratio while increased hydrogen peroxide (H2O2) production, GSSG, and protein carbonyl content, inducing oxidative stress (OS) in tumoral tissues. This imbalance between reactive oxygen species (ROS) and antioxidants was related to mitochondrial dysfunction and uncoupling, characterized by reduced mitochondrial respiratory parameters and dissipation of mitochondrial membrane potential (ΔΨm), respectively. Furthermore, GK-1 likely affected autophagy flux, confirmed by elevated levels of p62, a marker of autophagy flux. Overall, the induction of OS, dysfunction, and uncoupling of the mitochondria and the reduction of autophagy could be molecular mechanisms that underlie the reduction of the 4T1 breast cancer induced by GK-1.}, } @article {pmid36225907, year = {2022}, author = {Zhang, A and Xu, J and Xu, X and Wu, J and Li, P and Wang, B and Fang, H}, title = {Genome-wide identification and characterization of the KCS gene family in sorghum (Sorghum bicolor (L.) Moench).}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e14156}, pmid = {36225907}, issn = {2167-8359}, mesh = {*Sorghum/genetics ; Plant Proteins/genetics ; Phylogeny ; Regulatory Sequences, Nucleic Acid ; Promoter Regions, Genetic ; }, abstract = {The aboveground parts of plants are covered with cuticle, a hydrophobic layer composed of cutin polyester and cuticular wax that can protect plants from various environmental stresses. β-Ketoacyl-CoA synthase (KCS) is the key rate-limiting enzyme in plant wax synthesis. Although the properties of KCS family genes have been investigated in many plant species, the understanding of this gene family in sorghum is still limited. Here, a total of 25 SbKCS genes were identified in the sorghum genome, which were named from SbKCS1 to SbKCS25. Evolutionary analysis among different species divided the KCS family into five subfamilies and the SbKCSs were more closely related to maize, implying a closer evolutionary relationship between sorghum and maize. All SbKCS genes were located on chromosomes 1, 2, 3, 4, 5, 6, 9 and 10, respectively, while Chr 1 and Chr 10 contained more KCS genes than other chromosomes. The prediction results of subcellular localization showed that SbKCSs were mainly expressed in the plasma membrane and mitochondria. Gene structure analysis revealed that there was 0-1 intron in the sorghum KCS family and SbKCSs within the same subgroup were similar. Multiple cis-acting elements related to abiotic stress, light and hormone response were enriched in the promoters of SbKCS genes, which indicated the functional diversity among these genes. The three-dimensional structure analysis showed that a compact spherical space structure was formed by various secondary bonds to maintain the stability of SbKCS proteins, which was necessary for their biological activity. qRT-PCR results revealed that nine randomly selected SbKCS genes expressed differently under drought and salt treatments, among which SbKCS8 showed the greatest fold of expression difference at 12 h after drought and salt stresses, which suggested that the SbKCS genes played a potential role in abiotic stress responses. Taken together, these results provided an insight into investigating the functions of KCS family in sorghum and in response to abiotic stress.}, } @article {pmid36213509, year = {2022}, author = {Kotov, AA and Taylor, DJ}, title = {Daphnia japonica sp. nov. (Crustacea: Cladocera) an eastern Palearctic montane species with mitochondrial discordance.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e14113}, pmid = {36213509}, issn = {2167-8359}, mesh = {Animals ; *Cladocera/genetics ; Daphnia/genetics ; Phylogeny ; Mitochondria/genetics ; Genes, Mitochondrial ; DNA ; }, abstract = {The Daphnia longispina complex (Crustacea: Cladocera) contains several keystone freshwater species such as D. longispina O.F. Müller (D. rosea Sars is a junior synonym), D. galeata Sars, D. cucullata Sars, and D. dentifera Forbes. The complex is common throughout the Holarctic, but there are several geographic regions where local forms have been assigned to European species names based on a superficial morphological resemblance. Here we examine the species status of a form that was previously assigned to D. rosea from a montane bog pond on Honshu, Japan. We used two nuclear non-coding loci (nDNA), mitochondrial sequences (the ND2 protein-coding region) and morphology for evidence. The mitochondrial gene evidence supported the existence of a divergent lineage that is more closely related to D. galeata than to D. dentifera. However, morphology and the nuclear DNA data indicated a lineage that is most closely related to D. dentifera. As our evidence supported the existence of a cohesive divergent lineage, we described a new species, Daphnia japonica sp. nov. Recognition of local and subalpine diversity in this group is critical as ongoing anthropogenic disturbance has been associated with introductions, local extirpations, and hybridization.}, } @article {pmid36659315, year = {2017}, author = {Ye, LQ and Zhao, H and Zhou, HJ and Ren, XD and Liu, LL and Otecko, NO and Wang, ZB and Yang, MM and Zeng, L and Hu, XT and Yao, YG and Zhang, YP and Wu, DD}, title = {The RNA editome of Macaca mulatta and functional characterization of RNA editing in mitochondria.}, journal = {Science bulletin}, volume = {62}, number = {12}, pages = {820-830}, doi = {10.1016/j.scib.2017.05.021}, pmid = {36659315}, issn = {2095-9281}, abstract = {RNA editing was first discovered in mitochondrial RNA molecular. However, whether adenosine-to-inosine (A-to-I) RNA editing has functions in nuclear genes involved in mitochondria remains elusive. Here, we retrieved 707,246 A-to-I RNA editing sites in Macaca mulatta leveraging massive transcriptomes of 30 different tissues and genomes of nine tissues, together with the reported data, and found that A-to-I RNA editing occurred frequently in nuclear genes that have functions in mitochondria. The mitochondrial structure, the level of ATP production, and the expression of some key genes involved in mitochondrial function were dysregulated after knocking down the expression of ADAR1 and ADAR2, the key genes encoding the enzyme responsible for RNA editing. When investigating dynamic changes of RNA editing during brain development, an amino-acid-changing RNA editing site (I234/V) in MFN1, a mediator of mitochondrial fusion, was identified to be significantly correlated with age, and could influence the function of MFN1. When studying transcriptomes of brain disorder, we found that dysregulated RNA editing sites in autism were also enriched within genes having mitochondrial functions. These data indicated that RNA editing had a significant function in mitochondria via their influence on nuclear genes.}, } @article {pmid36656997, year = {2023}, author = {Opazo, JC and Vandewege, MW and Hoffmann, FG and Zavala, K and Meléndez, C and Luchsinger, C and Cavieres, VA and Vargas-Chacoff, L and Morera, FJ and Burgos, PV and Tapia-Rojas, C and Mardones, GA}, title = {How many sirtuin genes are out there? evolution of sirtuin genes in vertebrates with a description of a new family member.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msad014}, pmid = {36656997}, issn = {1537-1719}, abstract = {Studying the evolutionary history of gene families is a challenging and exciting task with a wide range of implications. In addition to exploring fundamental questions about the origin and evolution of genes, disentangling their evolution is also critical to those who do functional/structural studies to allow a deeper and more precise interpretation of their results in an evolutionary context. The sirtuin gene family is a group of genes that are involved in a variety of biological functions mostly related to aging. Their duplicative history is an open question, as well as the definition of the repertoire of sirtuin genes among vertebrates. Our results show a well-resolved phylogeny that represents an improvement in our understanding of the duplicative history of the sirtuin gene family. We identified a new sirtuin gene family member (SIRT3.2) that was apparently lost in the last common ancestor of amniotes but retained in all other groups of jawed vertebrates. According to our experimental analyses, elephant shark SIRT3.2 protein is located in mitochondria, the overexpression of which leads to an increase in cellular levels of ATP. Moreover, in vitro analysis demonstrated it has deacetylase activity being modulated in a similar way to mammalian SIRT3. Our results indicate that there are at least eight sirtuin paralogs among vertebrates and that all of them can be traced back to the last common ancestor of the group that existed between 676 and 615 millions of years ago.}, } @article {pmid36412071, year = {2023}, author = {Shimpi, GG and Bentlage, B}, title = {Ancient endosymbiont-mediated transmission of a selfish gene provides a model for overcoming barriers to gene transfer into animal mitochondrial genomes.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {2}, pages = {e2200190}, doi = {10.1002/bies.202200190}, pmid = {36412071}, issn = {1521-1878}, mesh = {Animals ; *Genome, Mitochondrial/genetics ; Gene Transfer, Horizontal/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Repetitive Sequences, Nucleic Acid/genetics ; Phylogeny ; Evolution, Molecular ; }, abstract = {In contrast to bilaterian animals, non-bilaterian mitochondrial genomes contain atypical genes, often attributed to horizontal gene transfer (HGT) as an ad hoc explanation. Although prevalent in plants, HGT into animal mitochondrial genomes is rare, lacking suitable explanatory models for their occurrence. HGT of the mismatch DNA repair gene (mtMutS) from giant viruses to octocoral (soft corals and their kin) mitochondrial genomes provides a model for how barriers to HGT to animal mitochondria may be overcome. A review of the available literature suggests that this HGT was mediated by an alveolate endosymbiont infected with a lysogenic phycodnavirus that enabled insertion of the homing endonuclease containing mtMutS into octocoral mitochondrial genomes. We posit that homing endonuclease domains and similar selfish elements play a crucial role in such inter-domain gene transfers. Understanding the role of selfish genetic elements in HGT has the potential to aid development of tools for manipulating animal mitochondrial DNA.}, } @article {pmid36651963, year = {2023}, author = {Moreira, F and Arenas, M and Videira, A and Pereira, F}, title = {Evolution of TOP1 and TOP1MT Topoisomerases in Chordata.}, journal = {Journal of molecular evolution}, volume = {}, number = {}, pages = {}, pmid = {36651963}, issn = {1432-1432}, abstract = {Type IB topoisomerases relax the torsional stress associated with DNA metabolism in the nucleus and mitochondria and constitute important molecular targets of anticancer drugs. Vertebrates stand out among eukaryotes by having two Type IB topoisomerases acting specifically in the nucleus (TOP1) and mitochondria (TOP1MT). Despite their major importance, the origin and evolution of these paralogues remain unknown. Here, we examine the molecular evolutionary processes acting on both TOP1 and TOP1MT in Chordata, taking advantage of the increasing number of available genome sequences. We found that both TOP1 and TOP1MT evolved under strong purifying selection, as expected considering their essential biological functions. Critical active sites, including those associated with resistance to anticancer agents, were found particularly conserved. However, TOP1MT presented a higher rate of molecular evolution than TOP1, possibly related with its specialized activity on the mitochondrial genome and a less critical role in cells. We could place the duplication event that originated the TOP1 and TOP1MT paralogues early in the radiation of vertebrates, most likely associated with the first round of vertebrate tetraploidization (1R). Moreover, our data suggest that cyclostomes present a specialized mitochondrial Type IB topoisomerase. Interestingly, we identified two missense mutations replacing amino acids in the Linker region of TOP1MT in Neanderthals, which appears as a rare event when comparing the genome of both species. In conclusion, TOP1 and TOP1MT differ in their rates of evolution, and their evolutionary histories allowed us to better understand the evolution of chordates.}, } @article {pmid36648250, year = {2023}, author = {Graham, AM and Barreto, FS}, title = {Myxozoans (Cnidaria) do not retain key oxygen-sensing and homeostasis toolkit genes.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evad003}, pmid = {36648250}, issn = {1759-6653}, abstract = {For aerobic organisms, both the Hypoxia-Inducible Factor pathway and the mitochondrial genomes are key players in regulating oxygen homeostasis. Recent work has suggested that these mechanisms are not as highly conserved as previously thought, prompting more surveys across animal taxonomic levels, which would permit testing of hypotheses about the ecological conditions facilitating evolutionary loss of such genes. Phylum Cnidaria is known to harbor wide variation in mitochondrial chromosome morphology, including the extreme example, in the Myxozoa, of mitochondrial genome loss. Because myxozoans are obligate endoparasites, frequently encountering hypoxic environments, we hypothesize that variation in environmental oxygen availability could be a key determinant in the evolution of metabolic gene networks associated with oxygen sensing, hypoxia response, and energy production. Here, we surveyed genomes and transcriptomes across 46 cnidarian species for the presence of HIF pathway members, as well as for an assortment of hypoxia, mitochondrial, and stress-response toolkit genes. We find that presence of the HIF pathway, as well as number of genes associated with mitochondria, hypoxia, and stress response, do not vary in parallel to mitochondrial genome morphology. More interestingly, we uncover evidence that myxozoans have lost the canonical HIF pathway repression machinery, potentially altering HIF pathway functionality to work under the specific conditions of their parasitic lifestyles. In addition, relative to other cnidarians, myxozoans show loss of large proportions of genes associated with the mitochondrion and involved in response to hypoxia and general stress. Our results provide additional evidence that the HIF regulatory machinery is evolutionarily labile and that variations in the canonical system have evolved in many animal groups.}, } @article {pmid36642905, year = {2022}, author = {Zhou, XQ and Ma, J and Wang, RY and Wang, RH and Wu, YQ and Yang, XY and Chen, YJ and Tang, XN and Sun, ET}, title = {[Bacterial community diversity in Dermatophagoides farinae using high-throughput sequencing].}, journal = {Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control}, volume = {34}, number = {6}, pages = {630-634}, doi = {10.16250/j.32.1374.2022105}, pmid = {36642905}, issn = {1005-6661}, mesh = {Humans ; Animals ; *Dermatophagoides farinae/genetics ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; High-Throughput Nucleotide Sequencing ; *Microbiota ; Phylogeny ; }, abstract = {OBJECTIVE: To investigate the bacterial community diversity in Dermatophagoides farinae.

METHODS: Laboratory-cultured D. farinae was collected, and the composition of microbial communities was determined by sequence analyses of the V4 region in the bacterial 16S ribosomal RNA (16S rRNA) gene on an Illumina PE250 high-throughput sequencing platform. Following quality control and filtering of the raw sequence files, valid reads were obtained and subjected to operational taxonomic units (OTU) clustering and analysis of the composition of microbial communities and alpha diversity index using the Usearch software, Silva database, and Mothur software.

RESULTS: A total of 187 616 valid reads were obtained, and 469 OTUs were clustered based on a sequence similarity of more than 97%. OTU annotation showed that the bacteria in D. farinae belonged to 26 phyla, 43 classes, 100 orders, 167 families and 284 genera. The bacteria in D. farinae were mainly annotated to five phyla of Proteobacteria, Firmicutes, Bacteroidota, Actinobacteriota, and Acidobacteriota, with Proteobacteria as the dominant phylum, and mainly annotated to five dominant genera of Ralstonia, norank-f-Mitochondria, Staphylococcus and Sphingomonas, with Wolbachia identified in the non-dominant genus.

CONCLUSIONS: A high diversity is identified in the composition of the bacterial community in D. farinae, and there are differences in bacterial community diversity and abundance among D. farinae.}, } @article {pmid36646908, year = {2023}, author = {Muñoz-Gómez, SA}, title = {Energetics and evolution of anaerobic microbial eukaryotes.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {36646908}, issn = {2058-5276}, abstract = {Mitochondria and aerobic respiration have been suggested to be required for the evolution of eukaryotic cell complexity. Aerobic respiration is several times more energetically efficient than fermentation. Moreover, aerobic respiration occurs at internalized mitochondrial membranes that are not constrained by a sublinear scaling with cell volume. However, diverse and complex anaerobic eukaryotes (for example, free-living and parasitic unicellular, and even small multicellular, eukaryotes) that exclusively rely on fermentation for energy generation have evolved repeatedly from aerobic ancestors. How do fermenting eukaryotes maintain their cell volumes and complexity while relying on such a low energy-yielding process? Here I propose that reduced rates of ATP generation in fermenting versus respiring eukaryotes are compensated for by longer cell cycles that satisfy lifetime energy demands. A literature survey and growth efficiency calculations show that fermenting eukaryotes divide approximately four to six times slower than aerobically respiring counterparts with similar cell volumes. Although ecological advantages such as competition avoidance offset lower growth rates and yields in the short term, fermenting eukaryotes inevitably have fewer physiological and ecological possibilities, which ultimately constrain their long-term evolutionary trajectories.}, } @article {pmid36636864, year = {2023}, author = {Achatz, TJ and Von Holten, ZS and Kipp, JW and Fecchio, A and LaFond, LR and Greiman, SE and Martens, JR and Tkach, VV}, title = {Phylogenetic relationships and further unknown diversity of diplostomids (Diplostomida: Diplostomidae) parasitic in kingfishers.}, journal = {Journal of helminthology}, volume = {97}, number = {}, pages = {e8}, doi = {10.1017/S0022149X22000852}, pmid = {36636864}, issn = {1475-2697}, support = {P20GM103442/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Phylogeny ; *Trematoda ; Fishes/parasitology ; Mitochondria ; Brazil ; }, abstract = {Kingfishers (Alcedinidae Rafinesque) are common inhabitants of wetlands and are known to be definitive hosts to a wide range of digeneans that parasitize fish as second intermediate hosts. Among these digeneans, members of the Diplostomidae Poirier, 1886 (diplostomids) are particularly common. Recent studies of diplostomids collected from kingfishers have revealed that they are probably more diverse than currently known. This particularly concerns the genera Crassiphiala Van Haitsma, 1925 and Uvulifer Yamaguti, 1934. In the present work, we studied seven diplostomid taxa from kingfishers in Brazil, the USA and the Philippines. Partial DNA sequences of the nuclear large ribosomal subunit (28S) and mitochondrial cytochrome c oxidase I (cox1) genes were obtained, and 28S sequences were used to study the phylogenetic interrelationships of these diplostomids. We provide the first DNA sequences from Uvulifer semicircumcisus Dubois et Rausch, 1950 and a member of Subuvulifer Dubois, 1952. Pseudocrassiphiala n. gen. is erected for a previously recognized species-level lineage of Crassiphiala and a new generic diagnosis of Crassiphiala is provided. Crassiphiala jeffreybelli n. sp., Crassiphiala wecksteini n. sp. and Pseudocrassiphiala tulipifera n. sp. are described, and a description of newly collected, high-quality specimens of Crassiphiala bulboglossa Van Haitsma, 1925 (the type-species of the genus) is provided.}, } @article {pmid36634115, year = {2023}, author = {Rossitto De Marchi, B and Gama, AB and Smith, HA}, title = {Evidence of the association between the Q2 mitochondrial group of Bemisia tabaci MED species (Hemiptera: Aleyrodidae) and low competitive displacement capability.}, journal = {PloS one}, volume = {18}, number = {1}, pages = {e0280002}, pmid = {36634115}, issn = {1932-6203}, mesh = {Animals ; Phylogeny ; *Hemiptera/genetics ; Mitochondria/genetics ; Food ; Florida ; }, abstract = {The whitefly, Bemisia tabaci (Gennadius), is one of the most serious agricultural pests worldwide. Bemisia tabaci is a cryptic species complex of more than 40 species among which the invasive MEAM1 and MED species are the most widespread and economically important. Both MEAM1 and MED present intraspecific genetic variability and some haplotypes are reported to be more invasive than others. MED can be further deconstructed into different genetic groups, including MED-Q1 and MED-Q2. However, distinct biological phenotypes discerning the different MED mitochondrial haplotypes are yet to be characterized. Competitive displacement and life-history trials were carried out between MED-Q2 and MEAM1 populations collected in Florida, USA. In addition, a phylogenetic analysis was carried out including populations from previous whitefly competitive displacement studies for identification and comparison of the MED mitochondrial groups. In contrast to other studies with MED-Q1, the MED-Q2 population from Florida is less likely to displace MEAM1 on pepper. In addition, both pepper and watermelon were a more favorable host to MEAM1 compared to MED-Q2 according to the life history trials.}, } @article {pmid35860045, year = {2022}, author = {Jamaludin, NA and Jamaluddin, JAF and Rahim, MA and Mohammed Akib, NA and Ratmuangkhwang, S and Mohd Arshaad, W and Mohd Nor, SA}, title = {Mitochondrial marker implies fishery separate management units for spotted sardinella, Amblygaster sirm (Walbaum, 1792) populations in the South China Sea and the Andaman Sea.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e13706}, pmid = {35860045}, issn = {2167-8359}, mesh = {Animals ; Phylogeny ; *Fisheries ; *Conservation of Natural Resources ; Mitochondria/genetics ; Fishes/genetics ; China ; }, abstract = {The spotted sardinella, Amblygaster sirm (Walbaum, 1792), is a commercial sardine commonly caught in Malaysia. Lack of management of these marine species in Malaysian waters could lead to overfishing and potentially declining fish stock populations. Therefore, sustainable management of this species is of paramount importance to ensure its longevity. As such, molecular information is vital in determining the A. sirm population structure and management strategy. In the present study, mitochondrial DNA Cytochrome b was sequenced from 10 A. sirm populations: the Andaman Sea (AS) (two), South China Sea (SCS) (six), Sulu Sea (SS) (one), and Celebes Sea (CS) (one). Accordingly, the intra-population haplotype diversity (Hd) was high (0.91-1.00), and nucleotide diversity (π) was low (0.002-0.009), which suggests a population bottleneck followed by rapid population growth. Based on the phylogenetic trees, minimum spanning network (MSN), population pairwise comparison, and F ST,and supported by analysis of molecular variance (AMOVA) and spatial analysis of molecular variance (SAMOVA) tests, distinct genetic structures were observed (7.2% to 7.6% genetic divergence) between populations in the SCS and its neighboring waters, versus those in the AS. Furthermore, the results defined A. sirm stock boundaries and evolutionary between the west and east coast (which shares the same waters as western Borneo) of Peninsular Malaysia. In addition, genetic homogeneity was revealed throughout the SCS, SS, and CS based on the non-significant F STpairwise comparisons. Based on the molecular evidence, separate management strategies may be required for A. sirm of the AS and the SCS, including its neighboring waters.}, } @article {pmid36634192, year = {2023}, author = {Osipova, E and Barsacchi, R and Brown, T and Sadanandan, K and Gaede, AH and Monte, A and Jarrells, J and Moebius, C and Pippel, M and Altshuler, DL and Winkler, S and Bickle, M and Baldwin, MW and Hiller, M}, title = {Loss of a gluconeogenic muscle enzyme contributed to adaptive metabolic traits in hummingbirds.}, journal = {Science (New York, N.Y.)}, volume = {379}, number = {6628}, pages = {185-190}, doi = {10.1126/science.abn7050}, pmid = {36634192}, issn = {1095-9203}, abstract = {Hummingbirds possess distinct metabolic adaptations to fuel their energy-demanding hovering flight, but the underlying genomic changes are largely unknown. Here, we generated a chromosome-level genome assembly of the long-tailed hermit and screened for genes that have been specifically inactivated in the ancestral hummingbird lineage. We discovered that FBP2 (fructose-bisphosphatase 2), which encodes a gluconeogenic muscle enzyme, was lost during a time period when hovering flight evolved. We show that FBP2 knockdown in an avian muscle cell line up-regulates glycolysis and enhances mitochondrial respiration, coincident with an increased mitochondria number. Furthermore, genes involved in mitochondrial respiration and organization have up-regulated expression in hummingbird flight muscle. Together, these results suggest that FBP2 loss was likely a key step in the evolution of metabolic muscle adaptations required for true hovering flight.}, } @article {pmid36632145, year = {2023}, author = {Borges, DGF and Carvalho, DS and Bomfim, GC and Ramos, PIP and Brzozowski, J and Góes-Neto, A and Andrade, R and El-Hani, C}, title = {On the origin of mitochondria: a multilayer network approach.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e14571}, pmid = {36632145}, issn = {2167-8359}, abstract = {BACKGOUND: The endosymbiotic theory is widely accepted to explain the origin of mitochondria from a bacterial ancestor. While ample evidence supports the intimate connection of Alphaproteobacteria to the mitochondrial ancestor, pinpointing its closest relative within sampled Alphaproteobacteria is still an open evolutionary debate. Many different phylogenetic methods and approaches have been used to answer this challenging question, further compounded by the heterogeneity of sampled taxa, varying evolutionary rates of mitochondrial proteins, and the inherent biases in each method, all factors that can produce phylogenetic artifacts. By harnessing the simplicity and interpretability of protein similarity networks, herein we re-evaluated the origin of mitochondria within an enhanced multilayer framework, which is an extension and improvement of a previously developed method.

METHODS: We used a dataset of eight proteins found in mitochondria (N = 6 organisms) and bacteria (N = 80 organisms). The sequences were aligned and resulting identity matrices were combined to generate an eight-layer multiplex network. Each layer corresponded to a protein network, where nodes represented organisms and edges were placed following mutual sequence identity. The Multi-Newman-Girvan algorithm was applied to evaluate community structure, and bifurcation events linked to network partition allowed to trace patterns of divergence between studied taxa.

RESULTS: In our network-based analysis, we first examined the topology of the 8-layer multiplex when mitochondrial sequences disconnected from the main alphaproteobacterial cluster. The resulting topology lent firm support toward an Alphaproteobacteria-sister placement for mitochondria, reinforcing the hypothesis that mitochondria diverged from the common ancestor of all Alphaproteobacteria. Additionally, we observed that the divergence of Rickettsiales was an early event in the evolutionary history of alphaproteobacterial clades.

CONCLUSION: By leveraging complex networks methods to the challenging question of circumscribing mitochondrial origin, we suggest that the entire Alphaproteobacteria clade is the closest relative to mitochondria (Alphaproteobacterial-sister hypothesis), echoing recent findings based on different datasets and methodologies.}, } @article {pmid36463410, year = {2023}, author = {Krynická, V and Skotnicová, P and Jackson, PJ and Barnett, S and Yu, J and Wysocka, A and Kaňa, R and Dickman, MJ and Nixon, PJ and Hunter, CN and Komenda, J}, title = {FtsH4 protease controls biogenesis of the PSII complex by dual regulation of high light-inducible proteins.}, journal = {Plant communications}, volume = {4}, number = {1}, pages = {100502}, doi = {10.1016/j.xplc.2022.100502}, pmid = {36463410}, issn = {2590-3462}, mesh = {Peptide Hydrolases ; Photosystem II Protein Complex/genetics/metabolism ; Phylogeny ; Thylakoids/metabolism ; Chloroplasts/metabolism ; *Arabidopsis/genetics/metabolism ; *Synechocystis/genetics/metabolism ; *Arabidopsis Proteins/genetics/metabolism ; Metalloproteases/genetics/metabolism ; }, abstract = {FtsH proteases are membrane-embedded proteolytic complexes important for protein quality control and regulation of various physiological processes in bacteria, mitochondria, and chloroplasts. Like most cyanobacteria, the model species Synechocystis sp. PCC 6803 contains four FtsH homologs, FtsH1-FtsH4. FtsH1-FtsH3 form two hetero-oligomeric complexes, FtsH1/3 and FtsH2/3, which play a pivotal role in acclimation to nutrient deficiency and photosystem II quality control, respectively. FtsH4 differs from the other three homologs by the formation of a homo-oligomeric complex, and together with Arabidopsis thaliana AtFtsH7/9 orthologs, it has been assigned to another phylogenetic group of unknown function. Our results exclude the possibility that Synechocystis FtsH4 structurally or functionally substitutes for the missing or non-functional FtsH2 subunit in the FtsH2/3 complex. Instead, we demonstrate that FtsH4 is involved in the biogenesis of photosystem II by dual regulation of high light-inducible proteins (Hlips). FtsH4 positively regulates expression of Hlips shortly after high light exposure but is also responsible for Hlip removal under conditions when their elevated levels are no longer needed. We provide experimental support for Hlips as proteolytic substrates of FtsH4. Fluorescent labeling of FtsH4 enabled us to assess its localization using advanced microscopic techniques. Results show that FtsH4 complexes are concentrated in well-defined membrane regions at the inner and outer periphery of the thylakoid system. Based on the identification of proteins that co-purified with the tagged FtsH4, we speculate that FtsH4 concentrates in special compartments in which the biogenesis of photosynthetic complexes takes place.}, } @article {pmid35808858, year = {2023}, author = {Cassidy-Hanley, DM and Doerder, FP and Hossain, M and Devine, C and Clark, T}, title = {Molecular identification of Tetrahymena species.}, journal = {The Journal of eukaryotic microbiology}, volume = {70}, number = {1}, pages = {e12936}, pmid = {35808858}, issn = {1550-7408}, support = {P40 OD010964/OD/NIH HHS/United States ; P40 OD010964/NH/NIH HHS/United States ; }, mesh = {*Tetrahymena/genetics ; Mitochondria/genetics ; DNA, Intergenic/genetics ; Phylogeny ; }, abstract = {Mitochondrial cox1 689 bp barcodes are routinely used for identification of Tetrahymena species. Here, we examine whether two shorter nuclear sequences, the 5.8S rRNA gene region and the intergenic region between H3 and H4 histone genes, might also be useful either singly or in combination with each other or cox1. We obtained sequences from ~300 wild isolates deposited at the Tetrahymena Stock Center and analyzed additional sequences obtained from GenBank. The 5.8S rRNA gene and portions of its transcribed flanks identify isolates as to their major clade and uniquely identify some, but not all, species. The ~330 bp H3/H4 intergenic region possesses low intraspecific variability and is unique for most species. However, it fails to distinguish between two pairs of common species and their rarer counterparts, and its use is complicated by the presence of duplicate genes in some species. The results show that while the cox1 sequence is the best single marker for Tetrahymena species identification, 5.8S rRNA, and the H3/H4 intergenic regions sequences are useful, singly or in combination, to confirm cox1 species assignments or as part of a preliminary survey of newly collected Tetrahymena. From our newly collected isolates, the results extend the biogeographical range of T. shanghaiensis and T. malaccensis and identify a new species, Tetrahymena arleneae n. sp. herein described.}, } @article {pmid35497189, year = {2022}, author = {Chen, Z and Schrödl, M}, title = {How many single-copy orthologous genes from whole genomes reveal deep gastropod relationships?.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e13285}, pmid = {35497189}, issn = {2167-8359}, mesh = {Animals ; *Gastropoda/genetics ; Phylogeny ; Mollusca ; Genome/genetics ; Transcriptome ; }, abstract = {The Gastropoda contains 80% of existing mollusks and is the most diverse animal class second only to the Insecta. However, the deep phylogeny of gastropods has been controversial for a long time. Especially the position of Patellogastropoda is a major uncertainty. Morphology and some mitochondria studies concluded that Patellogastropoda is likely to be sister to all other gastropods (Orthogastropoda hypothesis), while transcriptomic and other mitogenomic studies indicated that Patellogastropoda and Vetigastropoda are sister taxa (Psilogastropoda). With the release of high-quality genomes, orthologous genes can be better identified and serve as powerful candidates for phylogenetic analysis. The question is, given the current limitations on the taxon sampling side, how many markers are needed to provide robust results. Here, we identified single-copy orthologous genes (SOGs) from 14 gastropods species with whole genomes available which cover five main gastropod subclasses. We generated different datasets from 395 to 1610 SOGs by allowing species missing in different levels. We constructed gene trees of each SOG, and inferred species trees from different collections of gene trees. We found as the number of SOGs increased, the inferred topology changed from Patellogastropoda being sister to all other gastropods to Patellogastropoda being sister to Vetigastropoda + Neomphalina (Psilogastropoda s.l.), with considerable support. Our study thus rejects the Orthogastropoda concept showing that the selection of the representative species and use of sufficient informative sites greatly influence the analysis of deep gastropod phylogeny.}, } @article {pmid36629021, year = {2023}, author = {Fang, YK and Vaitová, Z and Hampl, V}, title = {A mitochondrion-free eukaryote contains proteins capable of import into an exogenous mitochondrion-related organelle.}, journal = {Open biology}, volume = {13}, number = {1}, pages = {220238}, doi = {10.1098/rsob.220238}, pmid = {36629021}, issn = {2046-2441}, abstract = {The endobiotic flagellate Monocercomonoides exilis is the only known eukaryote to have lost mitochondria and all its associated proteins in its evolutionary past. This final stage of the mitochondrial evolutionary pathway may serve as a model to explain events at their very beginning such as the initiation of protein import. We have assessed the capability of proteins from this eukaryote to enter emerging mitochondria using a specifically designed in vitro assay. Hydrogenosomes (reduced mitochondria) of Trichomonas vaginalis were incubated with a soluble protein pool derived from a cytosolic fraction of M. exilis, and proteins entering hydrogenosomes were subsequently detected by mass spectrometry. The assay detected 19 specifically and reproducibly imported proteins, and in 14 cases the import was confirmed by the overexpression of their tagged version in T. vaginalis. In most cases, only a small portion of the signal reached the hydrogenosomes, suggesting specific but inefficient transport. Most of these proteins represent enzymes of carbon metabolism, and none exhibited clear signatures of proteins targeted to hydrogenosomes or mitochondria, which is consistent with their inefficient import. The observed phenomenon may resemble a primaeval type of protein import which might play a role in the establishment of the organelle and shaping of its proteome in the initial stages of endosymbiosis.}, } @article {pmid36351770, year = {2022}, author = {Hénault, M and Marsit, S and Charron, G and Landry, CR}, title = {Hybridization drives mitochondrial DNA degeneration and metabolic shift in a species with biparental mitochondrial inheritance.}, journal = {Genome research}, volume = {32}, number = {11-12}, pages = {2043-2056}, doi = {10.1101/gr.276885.122}, pmid = {36351770}, issn = {1549-5469}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Genes, Mitochondrial ; Mitochondria/genetics ; Hybridization, Genetic ; Genotype ; Saccharomyces cerevisiae/genetics ; }, abstract = {Mitochondrial DNA (mtDNA) is a cytoplasmic genome that is essential for respiratory metabolism. Although uniparental mtDNA inheritance is most common in animals and plants, distinct mtDNA haplotypes can coexist in a state of heteroplasmy, either because of paternal leakage or de novo mutations. mtDNA integrity and the resolution of heteroplasmy have important implications, notably for mitochondrial genetic disorders, speciation, and genome evolution in hybrids. However, the impact of genetic variation on the transition to homoplasmy from initially heteroplasmic backgrounds remains largely unknown. Here, we use Saccharomyces yeasts, fungi with constitutive biparental mtDNA inheritance, to investigate the resolution of mtDNA heteroplasmy in a variety of hybrid genotypes. We previously designed 11 crosses along a gradient of parental evolutionary divergence using undomesticated isolates of Saccharomyces paradoxus and Saccharomyces cerevisiae Each cross was independently replicated 48 to 96 times, and the resulting 864 hybrids were evolved under relaxed selection for mitochondrial function. Genome sequencing of 446 MA lines revealed extensive mtDNA recombination, but the recombination rate was not predicted by parental divergence level. We found a strong positive relationship between parental divergence and the rate of large-scale mtDNA deletions, which led to the loss of respiratory metabolism. We also uncovered associations between mtDNA recombination, mtDNA deletion, and genome instability that were genotype specific. Our results show that hybridization in yeast induces mtDNA degeneration through large-scale deletion and loss of function, with deep consequences for mtDNA evolution, metabolism, and the emergence of reproductive isolation.}, } @article {pmid35480563, year = {2022}, author = {Di-Nizo, CB and Suárez-Villota, EY and Silva, MJJ}, title = {Species limits and recent diversification of Cerradomys (Sigmodontinae: Oryzomyini) during the Pleistocene.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e13011}, pmid = {35480563}, issn = {2167-8359}, mesh = {Animals ; *Sigmodontinae ; Phylogeny ; *Biological Evolution ; Mitochondria ; South America ; }, abstract = {Cerradomys is a genus of the tribe Oryzomyini with eight species currently recognized, and a controversial taxonomy. These species are mainly distributed in the South America dry diagonal, but some species extend into Atlantic Forest, reaching the coastal sandy plains known as Restingas. This study aimed to address species limits and patterns of diversification of Cerradomys species. For this purpose, we performed cytogenetic and molecular analyses (phylogeny, coalescent species delimitation, barcoding, and divergence times estimation) using multiple mitochondrial and nuclear markers on a comprehensive sampling, representing all nominal taxa reported so far. Chromosomal information was a robust marker recognizing eight Cerradomys species. Reciprocal monophyly was recovered for all the species, except for C. subflavus. These results together with coalescent analyses recovered eight species as the most congruent species delimitation scenario for the genus (mean C tax : 0.72). Divergence time estimates revealed that Cerradomys' diversification occurred about 1.32 million years ago (Mya) during the Pleistocene. Although our results conservatively support the eight Cerradomys species described so far, different lines of evidence suggest that C. langguthi and C. subflavus could potentially be species-complexes. We discussed this scenario in the light of multiple evolutionary processes within and between species and populations, since Cerradomys comprises a species group with recent diversification affected by Pleistocene climatic changes and by the complex biogeographic history of South America dry diagonal. This work supports that the diversity of Cerradomys is underestimated and reiterates that interdisciplinary approaches are mandatory to identify small rodent species properly, and to unhide cryptic species.}, } @article {pmid36463372, year = {2023}, author = {Nikelski, E and Rubtsov, AS and Irwin, D}, title = {High heterogeneity in genomic differentiation between phenotypically divergent songbirds: a test of mitonuclear co-introgression.}, journal = {Heredity}, volume = {130}, number = {1}, pages = {1-13}, pmid = {36463372}, issn = {1365-2540}, mesh = {Animals ; *Songbirds/genetics ; Genome ; Genomics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Phylogeny ; }, abstract = {Comparisons of genomic variation among closely related species often show more differentiation in mitochondrial DNA (mtDNA) and sex chromosomes than in autosomes, a pattern expected due to the differing effective population sizes and evolutionary dynamics of these genomic components. Yet, introgression can cause species pairs to deviate dramatically from general differentiation trends. The yellowhammer (Emberiza citrinella) and pine bunting (E. leucocephalos) are hybridizing avian sister species that differ greatly in appearance and moderately in nuclear DNA, but that show no mtDNA differentiation. This discordance is best explained by adaptive mtDNA introgression-a process that can select for co-introgression at nuclear genes with mitochondrial functions (mitonuclear genes). To better understand these discordant differentiation patterns and characterize nuclear differentiation in this system, we investigated genome-wide differentiation between allopatric yellowhammers and pine buntings and compared it to what was seen previously in mtDNA. We found significant nuclear differentiation that was highly heterogeneous across the genome, with a particularly wide differentiation peak on the sex chromosome Z. We further investigated mitonuclear gene co-introgression between yellowhammers and pine buntings and found support for this process in the direction of pine buntings into yellowhammers. Genomic signals indicative of co-introgression were common in mitonuclear genes coding for subunits of the mitoribosome and electron transport chain complexes. Such introgression of mitochondrial DNA and mitonuclear genes provides a possible explanation for the patterns of high genomic heterogeneity in genomic differentiation seen among some species groups.}, } @article {pmid36613565, year = {2022}, author = {Bottoni, P and Gionta, G and Scatena, R}, title = {Remarks on Mitochondrial Myopathies.}, journal = {International journal of molecular sciences}, volume = {24}, number = {1}, pages = {}, doi = {10.3390/ijms24010124}, pmid = {36613565}, issn = {1422-0067}, abstract = {Mitochondrial myopathies represent a heterogeneous group of diseases caused mainly by genetic mutations to proteins that are related to mitochondrial oxidative metabolism. Meanwhile, a similar etiopathogenetic mechanism (i.e., a deranged oxidative phosphorylation and a dramatic reduction of ATP synthesis) reveals that the evolution of these myopathies show significant differences. However, some physiological and pathophysiological aspects of mitochondria often reveal other potential molecular mechanisms that could have a significant pathogenetic role in the clinical evolution of these disorders, such as: i. a deranged ROS production both in term of signaling and in terms of damaging molecules; ii. the severe modifications of nicotinamide adenine dinucleotide (NAD)+/NADH, pyruvate/lactate, and α-ketoglutarate (α-KG)/2- hydroxyglutarate (2-HG) ratios. A better definition of the molecular mechanisms at the basis of their pathogenesis could improve not only the clinical approach in terms of diagnosis, prognosis, and therapy of these myopathies but also deepen the knowledge of mitochondrial medicine in general.}, } @article {pmid36610569, year = {2023}, author = {Ji, X and Tian, Y and Liu, W and Lin, C and He, F and Yang, J and Miao, W and Li, Z}, title = {Mitochondrial characteristics of the powdery mildew genus Erysiphe revealed an extraordinary evolution in protein-coding genes.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {123153}, doi = {10.1016/j.ijbiomac.2023.123153}, pmid = {36610569}, issn = {1879-0003}, abstract = {The genus Erysiphe was an obligate parasite causing powdery mildew disease on a wide range of higher plants. However, the knowledge of their mitogenome architecture for lifestyle adaptability was scarce. Here, we assembled the first complete mitogenome (190,559 bp in size) for rubber tree powdery mildew pathogen Erysiphe quercicola. Comparable analysis of the Erysiphe mitogenomes exhibited conserved gene content, genome organization and codon usage bias, but extensive dynamic intron gain/loss events were presented between Erysiphe species. The phylogeny of the Ascomycota species constructed in the phylogenetic analysis showed genetic divergences of the Erysiphe species. Compared with other distant saprophytic and plant pathogenic fungi, Erysiphe had a flat distribution of evolutionary pressures on fungal standard protein-coding genes (PCGs). The Erysiphe PCGs had the highest mean selection pressure. In particular, Erysiphe's cox1, nad1, cob and rps3 genes had the most elevated selection pressures among corresponding PCGs across fungal genera. Altogether, the investigations provided a novel insight into the potential evolutionary pattern of the genus Erysiphe to adapt obligate biotrophic lifestyle and promoted the understanding of the high plasticity and population evolution of fungal mitogenomes.}, } @article {pmid36605953, year = {2022}, author = {Wu, CS and Chen, CI and Chaw, SM}, title = {Plastid phylogenomics and plastome evolution in the morning glory family (Convolvulaceae).}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {1061174}, pmid = {36605953}, issn = {1664-462X}, abstract = {Convolvulaceae, the morning glories or bindweeds, is a large family containing species of economic value, including crops, traditional medicines, ornamentals, and vegetables. However, not only are the phylogenetic relationships within this group still debated at the intertribal and intergeneric levels, but also plastid genome (plastome) complexity within Convolvulaceae is not well surveyed. We gathered 78 plastomes representing 17 genera across nine of the 12 Convolvulaceae tribes. Our plastid phylogenomic trees confirm the monophyly of Convolvulaceae, place the genus Jacquemontia within the subfamily Dicranostyloideae, and suggest that the tribe Merremieae is paraphyletic. In contrast, positions of the two genera Cuscuta and Erycibe are uncertain as the bootstrap support of the branches leading to them is moderate to weak. We show that nucleotide substitution rates are extremely variable among Convolvulaceae taxa and likely responsible for the topological uncertainty. Numerous plastomic rearrangements are detected in Convolvulaceae, including inversions, duplications, contraction and expansion of inverted repeats (IRs), and losses of genes and introns. Moreover, integrated foreign DNA of mitochondrial origin was found in the Jacquemontia plastome, adding a rare example of gene transfer from mitochondria to plastids in angiosperms. In the IR of Dichondra, we discovered an extra copy of rpl16 containing a direct repeat of ca. 200 bp long. This repeat was experimentally demonstrated to trigger effective homologous recombination, resulting in the coexistence of intron-containing and -lacking rpl16 duplicates. Therefore, we propose a hypothetical model to interpret intron loss accompanied by invasion of direct repeats at appropriate positions. Our model complements the intron loss model driven by retroprocessing when genes have lost introns but contain abundant RNA editing sites adjacent to former splicing sites.}, } @article {pmid36605941, year = {2022}, author = {Locatelli, AG and Cenci, S}, title = {Autophagy and longevity: Evolutionary hints from hyper-longevous mammals.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {1085522}, pmid = {36605941}, issn = {1664-2392}, abstract = {Autophagy is a fundamental multi-tasking adaptive cellular degradation and recycling strategy. Following its causal implication in age-related decline, autophagy is currently among the most broadly studied and challenged mechanisms within aging research. Thanks to these efforts, new cellular nodes interconnected with this phylogenetically ancestral pathway and unexpected roles of autophagy-associated genetic products are unveiled daily, yet the history of functional adaptations of autophagy along its evolutive trail is poorly understood and documented. Autophagy is traditionally studied in canonical and research-wise convenient model organisms such as yeast and mice. However, unconventional animal models endowed with extended longevity and exemption from age-related diseases offer a privileged perspective to inquire into the role of autophagy in the evolution of longevity. In this mini review we retrace the appearance and functions evolved by autophagy in eukaryotic cells and its protective contribution in the pathophysiology of aging.}, } @article {pmid35187492, year = {2022}, author = {Juhaszova, M and Kobrinsky, E and Zorov, DB and Nuss, HB and Yaniv, Y and Fishbein, KW and de Cabo, R and Montoliu, L and Gabelli, SB and Aon, MA and Cortassa, S and Sollott, SJ}, title = {ATP Synthase K[+]- and H[+]-fluxes Drive ATP Synthesis and Enable Mitochondrial K[+]-"Uniporter" Function: II. Ion and ATP Synthase Flux Regulation.}, journal = {Function (Oxford, England)}, volume = {3}, number = {2}, pages = {zqac001}, pmid = {35187492}, issn = {2633-8823}, mesh = {Bayes Theorem ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism ; Phylogeny ; *Mitochondrial Proton-Translocating ATPases/genetics ; *Mitochondria/metabolism ; Adenosine Triphosphate/metabolism ; }, abstract = {We demonstrated that ATP synthase serves the functions of a primary mitochondrial K[+] "uniporter," i.e., the primary way for K[+] to enter mitochondria. This K[+] entry is proportional to ATP synthesis, regulating matrix volume and energy supply-vs-demand matching. We show that ATP synthase can be upregulated by endogenous survival-related proteins via IF1. We identified a conserved BH3-like domain of IF1 which overlaps its "minimal inhibitory domain" that binds to the β-subunit of F1. Bcl-xL and Mcl-1 possess a BH3-binding-groove that can engage IF1 and exert effects, requiring this interaction, comparable to diazoxide to augment ATP synthase's H[+] and K[+] flux and ATP synthesis. Bcl-xL and Mcl-1, but not Bcl-2, serve as endogenous regulatory ligands of ATP synthase via interaction with IF1 at this BH3-like domain, to increase its chemo-mechanical efficiency, enabling its function as the recruitable mitochondrial KATP-channel that can limit ischemia-reperfusion injury. Using Bayesian phylogenetic analysis to examine potential bacterial IF1-progenitors, we found that IF1 is likely an ancient (∼2 Gya) Bcl-family member that evolved from primordial bacteria resident in eukaryotes, corresponding to their putative emergence as symbiotic mitochondria, and functioning to prevent their parasitic ATP consumption inside the host cell.}, } @article {pmid35111395, year = {2022}, author = {Yuan, Z and Jiang, W and Sha, Z}, title = {A review of the common crab genus Macromedaeus Ward, 1942 (Brachyura, Xanthidae) from China Seas with description of a new species using integrative taxonomy methods.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e12735}, pmid = {35111395}, issn = {2167-8359}, mesh = {Animals ; Male ; *Brachyura/anatomy & histology ; Phylogeny ; Oceans and Seas ; Mitochondria ; China ; }, abstract = {Macromedaeus is one of the most common xanthid genera in shallow waters of the Indo-West Pacific. In this study, we describe a new species, Macromedaeus hainanensis sp. nov., and report on two newly recorded species, M. quinquedentatus (Krauss, 1843) and M. orientalis (Takeda & Miyake, 1969) from Hainan Island, South China Sea. M. hainanensis is most related to M. distinguendus (De Haan, 1833-1850) and M. orientalis on the carapace shape and granular appearance, but can be distinguished by unique morphological characteristics especially its front, pereopods and male first gonopod. Taxonomic identities of the six Macromedaeus species recorded from China seas are discussed, and a phylogenetic analyzation is performed on Macromedaeus and related taxa based on three mitochondrial and two nuclear markers (12S, 16S, COI, H3, 18S). Integrated taxonomic evidence is used to support the taxonomic status of each species.}, } @article {pmid36403761, year = {2023}, author = {Shi, F and Yu, T and Xu, Y and Zhang, S and Niu, Y and Ge, S and Tao, J and Zong, S}, title = {Comparative mitochondrial genomic analysis provides new insights into the evolution of the subfamily Lamiinae (Coleoptera: Cerambycidae).}, journal = {International journal of biological macromolecules}, volume = {225}, number = {}, pages = {634-647}, doi = {10.1016/j.ijbiomac.2022.11.125}, pmid = {36403761}, issn = {1879-0003}, mesh = {Animals ; *Coleoptera/genetics ; Phylogeny ; Mitochondria/genetics ; RNA, Transfer/genetics ; Genomics ; }, abstract = {The genus Monochamus within the subfamily Lamiinae is the main vector of Bursaphelenchus xylophilus, which causes pine wilt disease and induces substantial economic and ecological losses. Only three complete mitochondrial genomes of the genus Monochamus have been sequenced to date, and no comparative mitochondrial genomic studies of Lamiinae have been conducted. Here, the mitochondrial genomes of two Monochamus species, M. saltuarius and M. urussovi, were newly sequenced and annotated. The composition and order of genes in the mitochondrial genomes of Monochamus species are conserved. All transfer RNAs exhibit the typical clover-leaf secondary structure, with the exception of trnS1. Similar to other longhorn beetles, Lamiinae mitochondrial genomes have an A + T bias. All 13 protein-coding genes have experienced purifying selection, and tandem repeat sequences are abundant in the A + T-rich region. Phylogenetic analyses revealed congruent topologies among trees inferred from the five datasets, with the monophyly of Acanthocinini, Agapanthiini, Batocerini, Dorcaschematini, Pteropliini, and Saperdini receiving high support. The findings of this study enhance our understanding of mitochondrial genome evolution and will provide a basis for future studies of population genetics and phylogenetic investigations in this group.}, } @article {pmid36470482, year = {2023}, author = {Liu, J and Ni, Y and Liu, C}, title = {Polymeric structure of the Cannabis sativa L. mitochondrial genome identified with an assembly graph model.}, journal = {Gene}, volume = {853}, number = {}, pages = {147081}, doi = {10.1016/j.gene.2022.147081}, pmid = {36470482}, issn = {1879-0038}, mesh = {*Genome, Mitochondrial/genetics ; *Cannabis/genetics ; Plant Breeding ; *Genome, Chloroplast ; Repetitive Sequences, Nucleic Acid ; DNA, Mitochondrial/genetics ; Phylogeny ; Evolution, Molecular ; }, abstract = {Cannabis sativa L. belongs to the family Cannabaceae in Rosales. It has been widely used as medicines, building materials, and textiles. Elucidating its genome is critical for molecular breeding and synthetic biology study. Many studies have shown that the mitochondrial genomes (mitogenomes) and even chloroplast genomes (plastomes) had complex polymeric structures. Using the Nanopore sequencing platform, we sequenced, assembled, and analyzed its mitogenome and plastome. The resulting unitig graph suggested that the mitogenome had a complex polymeric structure. However, a gap-free, circular sequence was further assembled from the unitig graph. In contrast, a circular sequence representing the plastome was obtained. The mitogenome major conformation was 415,837 bp long, and the plastome was 153,927 bp long. To test if the repeat sequences promote recombination, which corresponds to the branch points in the structure, we tested the sequences around repeats by long-read mapping. Among 208 pairs of predicted repeats, the mapping results supported the presence of cross-over around 25 pairs of repeats. Subsequent PCR amplification confirmed the presence of cross-over around 15 of the 25 repeats. By comparing the mitogenome and plastome sequences, we identified 19 mitochondria plastid DNAs, including seven complete genes (trnW-CCA, trnP-UGG, psbJ, trnN-GUU, trnD-GUC, trnH-GUG, trnM-CAU) and nine gene fragments. Furthermore, the selective pressure analysis results showed that five genes (atp1, ccmB, ccmC, cox1, nad7) had 19 positively selected sites. Lastly, we predicted 28 RNA editing sites. A total of 8 RNA editing sites located in the coding regions were successfully validated by PCR amplification and Sanger sequencing, of which four were synonymous, and four were nonsynonymous. In particular, the RNA editing events appeared to be tissue-specific in C. sativa mitogenome. In summary, we have confirmed the major confirmation of C. sativa mitogenome and characterized its structural features in detail. These results provide critical information for future variety breeding and resource development for C. sativa.}, } @article {pmid36574824, year = {2022}, author = {Baião, GC and Schneider, DI and Miller, WJ and Klasson, L}, title = {Multiple introgressions shape mitochondrial evolutionary history in Drosophila paulistorum and the Drosophila willistoni group.}, journal = {Molecular phylogenetics and evolution}, volume = {}, number = {}, pages = {107683}, doi = {10.1016/j.ympev.2022.107683}, pmid = {36574824}, issn = {1095-9513}, abstract = {Hybridization and the consequent introgression of genomic elements is an important source of genetic diversity for biological lineages. This is particularly evident in young clades in which hybrid incompatibilities are still incomplete and mixing between species is more likely to occur. Drosophila paulistorum, a representative of the Neotropical Drosophila willistoni subgroup, is a classic model of incipient speciation. The species is divided into six semispecies that show varying degrees of pre- and post-mating incompatibility with each other. In the present study, we investigate the mitochondrial evolutionary history of D. paulistorum and the willistoni subgroup. For that, we perform phylogenetic and comparative analyses of the complete mitochondrial genomes and draft nuclear assemblies of 25 Drosophila lines of the willistoni and saltans species groups. Our results show that the mitochondria of D. paulistorum are polyphyletic and form two non-sister clades that we name α and β. Identification and analyses of nuclear mitochondrial insertions further reveal that the willistoni subgroup has an α-like mitochondrial ancestor and strongly suggest that both the α and β mitochondria of D. paulistorum were acquired through introgression from unknown fly lineages of the willistoni subgroup. We also uncover multiple mitochondrial introgressions across D. paulistorum semispecies and generate novel insight into the evolution of the species.}, } @article {pmid36553495, year = {2022}, author = {Kunerth, HD and Tapisso, JT and Valente, R and Mathias, MDL and Alves, PC and Searle, JB and Vega, R and Paupério, J}, title = {Characterising Mitochondrial Capture in an Iberian Shrew.}, journal = {Genes}, volume = {13}, number = {12}, pages = {}, pmid = {36553495}, issn = {2073-4425}, mesh = {Animals ; Phylogeny ; *Shrews/genetics ; *Chromosomes ; Mitochondria/genetics ; Spain ; }, abstract = {Mitochondrial introgression raises questions of biogeography and of the extent of reproductive isolation and natural selection. Previous phylogenetic work on the Sorex araneus complex revealed apparent mitonuclear discordance in Iberian shrews, indicating past hybridisation of Sorex granarius and the Carlit chromosomal race of S. araneus, enabling introgression of the S. araneus mitochondrial genome into S. granarius. To further study this, we genetically typed 61 Sorex araneus/coronatus/granarius from localities in Portugal, Spain, France, and Andorra at mitochondrial, autosomal, and sex-linked loci and combined our data with the previously published sequences. Our data are consistent with earlier data indicating that S. coronatus and S. granarius are the most closely related of the three species, confirming that S. granarius from the Central System mountain range in Spain captured the mitochondrial genome from a population of S. araneus. This mitochondrial capture event can be explained by invoking a biogeographical scenario whereby S. araneus was in contact with S. granarius during the Younger Dryas in central Iberia, despite the two species currently having disjunct distributions. We discuss whether selection favoured S. granarius with an introgressed mitochondrial genome. Our data also suggest recent hybridisation and introgression between S. coronatus and S. granarius, as well as between S. araneus and S. coronatus.}, } @article {pmid36555867, year = {2022}, author = {Malnick, SDH and Alin, P and Somin, M and Neuman, MG}, title = {Fatty Liver Disease-Alcoholic and Non-Alcoholic: Similar but Different.}, journal = {International journal of molecular sciences}, volume = {23}, number = {24}, pages = {}, pmid = {36555867}, issn = {1422-0067}, abstract = {In alcohol-induced liver disease (ALD) and in non-alcoholic fatty liver disease (NAFLD), there are abnormal accumulations of fat in the liver. This phenomenon may be related to excessive alcohol consumption, as well as the combination of alcohol consumption and medications. There is an evolution from simple steatosis to steatohepatitis, fibrosis and cirrhosis leading to hepatocellular carcinoma (HCC). Hepatic pathology is very similar regarding non-alcoholic fatty liver disease (NAFLD) and ALD. Initially, there is lipid accumulation in parenchyma and progression to lobular inflammation. The morphological changes in the liver mitochondria, perivenular and perisinusoidal fibrosis, and hepatocellular ballooning, apoptosis and necrosis and accumulation of fibrosis may lead to the development of cirrhosis and HCC. Medical history of ethanol consumption, laboratory markers of chronic ethanol intake, AST/ALT ratio on the one hand and features of the metabolic syndrome on the other hand, may help in estimating the contribution of alcohol intake and the metabolic syndrome, respectively, to liver steatosis.}, } @article {pmid36543927, year = {2022}, author = {Cunha, RL and Faleh, AB and Francisco, S and Šanda, R and Vukić, J and Corona, L and Dia, M and Glavičić, I and Kassar, A and Castilho, R and Robalo, JI}, title = {Three mitochondrial lineages and no Atlantic-Mediterranean barrier for the bogue Boops boops across its widespread distribution.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22124}, pmid = {36543927}, issn = {2045-2322}, mesh = {Humans ; Animals ; Phylogeny ; Phylogeography ; Azores ; Portugal ; *Mitochondria ; *Perciformes/genetics ; Atlantic Ocean ; Genetic Variation ; Mediterranean Sea ; }, abstract = {Marine species exhibiting wide distributional ranges are frequently subdivided into discrete genetic units over limited spatial scales. This is often due to specific life-history traits or oceanographic barriers that prevent gene flow. Fine-scale sampling studies revealed distinct phylogeographic patterns in the northeastern Atlantic and the Mediterranean, ranging from panmixia to noticeable population genetic structure. Here, we used mitochondrial sequence data to analyse connectivity in the bogue Boops boops throughout most of its widespread distribution. Our results identified the existence of three clades, one comprising specimens from the Azores and eastern Atlantic/Mediterranean, another with individuals from the Canary Islands, Madeira and Cape Verde archipelagos, and the third with samples from Mauritania only. One of the branches of the northern subtropical gyre (Azores Current) that drifts towards the Gulf of Cádiz promotes a closer connection between the Azores, southern Portugal and the Mediterranean B. boops populations. The Almería-Oran Front, widely recognised as an oceanographic barrier for many organisms to cross the Atlantic-Mediterranean divide, does not seem to affect the dispersal of this benthopelagic species. The southward movement of the Cape Verde Frontal Zone during the winter, combined with the relatively short duration of the pelagic larval stage of B. boops, may be potential factors for preventing the connectivity between the Atlantic oceanic archipelagos and Mauritania shaping the genetic signature of this species.}, } @article {pmid36543798, year = {2022}, author = {Zawal, A and Skuza, L and Michoński, G and Bańkowska, A and Szućko-Kociuba, I and Gastineau, R}, title = {Complete mitochondrial genome of Hygrobates turcicus Pešić, Esen & Dabert, 2017 (Acari, Hydrachnidia, Hygrobatoidea).}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22063}, pmid = {36543798}, issn = {2045-2322}, mesh = {Animals ; Female ; Male ; *Acari/genetics ; *Genome, Mitochondrial ; Mitochondria/genetics ; Codon, Initiator ; RNA, Ribosomal/genetics ; Phylogeny ; Sequence Analysis, DNA ; RNA, Transfer/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {The aim of the study was sequencing of the mitogenome of Hygrobates turcicus Pešić, Esen & Dabert, 2017 to expand knowledge of the polymorphism and cryptic or pseudocryptic diversity within Hydrachnidia. The samples originated from Bulgaria, Vidima River near Debnewo, 42°56'41.4''N, 24°48'44.6''E, depth 0.4 m, stones on the bottom, water flow 0.71 m/s, temperature 10 °C, pH 8.53, oxygen 110%, conductivity 279 µS/cm, hardness 121 CaO mg/l; 11 males, 27 females, 2 deutonymphs 12.x.2019 leg. Zawal, Michoński & Bańkowska; one male and one female dissected and slides mounted. The study was carried out using the following methods: DNA extraction, sequencing, assembly and annotation, comparison with other populations of H. turcicus, and multigene phylogeny. As a result of the study, it was determined that the mitogenome is 15,006 bp long and encodes for 13 proteins, 2 rRNAs, and 22 tRNAs. The genome is colinear with those of H. longiporus and H. taniguchii, the difference in size originating from a non-coding region located between protein-coding genes ND4L and ND3. Five genes have alternative start-codon, and four display premature termination. The multigene phylogeny obtained using all mitochondrial protein-coding genes unambiguously associates H. turcicus with the cluster formed by H. longiporus and H. taniguchii.}, } @article {pmid36545736, year = {2022}, author = {He, L and Maheshwari, A}, title = {Mitochondria in Early Life.}, journal = {Current pediatric reviews}, volume = {}, number = {}, pages = {}, doi = {10.2174/1573396319666221221110728}, pmid = {36545736}, issn = {1875-6336}, abstract = {Mitochondria are highly-dynamic, membrane-bound organelles that generate most of the chemical energy needed to power the biochemical reactions in eukaryotic cells. These organelles also communicate with the nucleus and other cellular structures to help maintain somatic homeostasis, allow cellular adaptation to stress, and help maintain the developmental trajectory. Mitochondria also perform numerous other functions to support metabolic, energetic, and epigenetic regulation in our cells. There is increasing information on various disorders caused by defects in intrinsic mitochondrial or supporting nuclear genes in different organ systems. In this review, we have summarized the ultrastructural morphology, structural components, our current understanding of the evolution, biogenesis, dynamics, function, clinical manifestations of mitochondrial dysfunction, and future possibilities. The implications of deficits in mitochondrial dynamics and signaling for embryo viability and offspring health are also explored. We present information from our own clinical and laboratory research in conjunction with information collected from an extensive search in the databases PubMed, EMBASE, and Scopus.}, } @article {pmid36527364, year = {2022}, author = {Knoop, V}, title = {C-to-U and U-to-C: RNA editing in plant organelles and beyond.}, journal = {Journal of experimental botany}, volume = {}, number = {}, pages = {}, doi = {10.1093/jxb/erac488}, pmid = {36527364}, issn = {1460-2431}, abstract = {The genomes in the two energy-converting organelles of plant cells, chloroplasts and mitochondria, contain numerous "errors" that are corrected at the level of RNA transcript copies. The genes encoded in the two endosymbiotic organelles would not function properly if their transcripts would not be altered by site-specific cytidine-to-uridine exchanges and by additional reverse U-to-C exchanges in hornworts, lycophytes and ferns. These peculiar processes of plant RNA editing, re-establishing genetic information that could alternatively be present at the organelle genome level, has spurred much research over more than 30 years. Lately this has revealed numerous interesting insights, notably on the biochemical machinery identifying specific pyrimidine nucleobases for conversion from C to U and vice versa. Here, I will summarize prominent research findings that have lately contributed to our better understanding of these phenomena introducing an added layer of information processing in plant cells. Some of this recent progress is based on the successful functional expression of plant RNA editing factors in bacteria and mammalian cells. These research approaches have recapitulated natural processes of horizontal gene transfer through which some protist lineages seem to have acquired plant RNA editing factors and adapted them functionally for their own purposes.}, } @article {pmid36523555, year = {2022}, author = {Hogg, DW and Reid, AL and Dodsworth, TL and Chen, Y and Reid, RM and Xu, M and Husic, M and Biga, PR and Slee, A and Buck, LT and Barsyte-Lovejoy, D and Locke, M and Lovejoy, DA}, title = {Skeletal muscle metabolism and contraction performance regulation by teneurin C-terminal-associated peptide-1.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {1031264}, pmid = {36523555}, issn = {1664-042X}, abstract = {Skeletal muscle regulation is responsible for voluntary muscular movement in vertebrates. The genes of two essential proteins, teneurins and latrophilins (LPHN), evolving in ancestors of multicellular animals form a ligand-receptor pair, and are now shown to be required for skeletal muscle function. Teneurins possess a bioactive peptide, termed the teneurin C-terminal associated peptide (TCAP) that interacts with the LPHNs to regulate skeletal muscle contractility strength and fatigue by an insulin-independent glucose importation mechanism in rats. CRISPR-based knockouts and siRNA-associated knockdowns of LPHN-1 and-3 in the C2C12 mouse skeletal cell line shows that TCAP stimulates an LPHN-dependent cytosolic Ca[2+] signal transduction cascade to increase energy metabolism and enhance skeletal muscle function via increases in type-1 oxidative fiber formation and reduce the fatigue response. Thus, the teneurin/TCAP-LPHN system is presented as a novel mechanism that regulates the energy requirements and performance of skeletal muscle.}, } @article {pmid36520311, year = {2023}, author = {Marszalek, J and Craig, EA and Tomiczek, B}, title = {J-Domain Proteins Orchestrate the Multifunctionality of Hsp70s in Mitochondria: Insights from Mechanistic and Evolutionary Analyses.}, journal = {Sub-cellular biochemistry}, volume = {101}, number = {}, pages = {293-318}, pmid = {36520311}, issn = {0306-0225}, mesh = {*Saccharomyces cerevisiae Proteins/metabolism ; HSP70 Heat-Shock Proteins/genetics/metabolism ; Mitochondria/genetics/metabolism ; Molecular Chaperones/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; }, abstract = {Mitochondrial J-domain protein (JDP) co-chaperones orchestrate the function of their Hsp70 chaperone partner(s) in critical organellar processes that are essential for cell function. These include folding, refolding, and import of mitochondrial proteins, maintenance of mitochondrial DNA, and biogenesis of iron-sulfur cluster(s) (FeS), prosthetic groups needed for function of mitochondrial and cytosolic proteins. Consistent with the organelle's endosymbiotic origin, mitochondrial Hsp70 and the JDPs' functioning in protein folding and FeS biogenesis clearly descended from bacteria, while the origin of the JDP involved in protein import is less evident. Regardless of their origin, all mitochondrial JDP/Hsp70 systems evolved unique features that allowed them to perform mitochondria-specific functions. Their modes of functional diversification and specialization illustrate the versatility of JDP/Hsp70 systems and inform our understanding of system functioning in other cellular compartments.}, } @article {pmid36519158, year = {2022}, author = {Kim, S and Eom, H and Nandre, R and Choi, YJ and Lee, H and Ryu, H and Ro, HS}, title = {Comparative structural analysis on the mitochondrial DNAs from various strains of Lentinula edodes.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1034387}, pmid = {36519158}, issn = {1664-302X}, abstract = {The evolution of mitochondria through variations in mitochondrial DNA (mtDNA) is one of the intriguing questions in eukaryotic cells. In order to assess the causes of the variations in mitochondria, the mtDNAs of the 21 strains of Lentinula edodes were assembled for this study, and analyzed together with four published mtDNA sequences. The mtDNAs were within the sizes of 117 kb ~ 122 kb. The gene number was observed consistent except for two mtDNAs, which carry a duplicated trnG1-trnG2 unit or a putative gene deletion. The size variation was largely attributed to the number of introns, repeated sequences, transposable elements (TEs), and plasmid-related sequences. Intron loss and gain were found from cox1, rnl, and rns of three mtDNAs. Loss of two introns in cox1 of KY217797.1 reduced its size by 2.7 kb, making it the smallest cox1 gene (8.4 kb) among the cox1s of the 25 mtDNAs, whereas gain of a Group II intron (2.65 kb) and loss of a Group I intron (1.7 kb) in cox1 of MF774813.1 resulted in the longest cox1 (12 kb). In rnl of L. edodes, we discovered four intron insertion consensus sequences which were unique to basidiomycetes but not ascomycetes. Differential incorporation of introns was the primary cause of the rnl size polymorphism. Homing endonucleases (HEGs) were suggestively involved in the mobilization of the introns because all of the introns have HEG genes of the LAGRIDADG or GIY-YIG families with the conserved HEG cleavage sites. TEs contributed to 11.04% of the mtDNA size in average, of which 7.08% was LTR-retrotransposon and 3.96% was DNA transposon, whereas the repeated sequences covered 4.6% of the mtDNA. The repeat numbers were variable in a strain-dependent manner. Both the TEs and repeated sequences were mostly found in the intronic and intergenic regions. Lastly, two major deletions were found in the plasmid-related sequence regions (pol2-pol3 and pol1-atp8) in the five mtDNAs. Particularly, the 6.8 kb-long deletion at pol2-pol3 region made MF774813.1 the shortest mtDNA of all. Our results demonstrate that mtDNA is a dynamic molecule that persistently evolves over a short period of time by insertion/deletion and repetition of DNA segments at the strain level.}, } @article {pmid36512580, year = {2022}, author = {Guo, S and Lin, X and Song, N}, title = {Mitochondrial phylogenomics reveals deep relationships of scarab beetles (Coleoptera, Scarabaeidae).}, journal = {PloS one}, volume = {17}, number = {12}, pages = {e0278820}, pmid = {36512580}, issn = {1932-6203}, mesh = {Animals ; Phylogeny ; *Coleoptera/genetics ; *Genome, Mitochondrial ; Mitochondria/genetics ; Base Sequence ; }, abstract = {In this study, we newly sequenced the complete mitochondrial genomes (mitogenomes) of two phytophagous scarab beetles, and investigated the deep level relationships within Scarabaeidae combined with other published beetle mitogenome sequences. The complete mitogenomes of Dicronocephalus adamsi Pascoe (Cetoniinae) and Amphimallon sp. (Melolonthinae) are 15,563 bp and 17,433 bp in size, respectively. Both mitogenomes have the typical set of 37 genes (13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes) and an A+T-rich region, with the same gene arrangement found in the majority of beetles. The secondary structures for ribosomal RNA genes (rrnL and rrnS) were inferred by comparative analysis method. Results from phylogenetic analyses provide support for major lineages and current classification of Scarabaeidae. Amino acid data recovered Scarabaeidae as monophyletic. The Scarabaeidae was split into two clades. One clade contained the subfamilies Scarabaeinae and Aphodiinae. The other major clade contained the subfamilies Dynastinae, Rutelinae, Cetoniinae, Melolonthinae and Sericini. The monophyly of Scarabaeinae, Aphodiinae, Dynastinae, Cetoniinae and Sericini were strongly supported. The Scarabaeinae was the sister group of Aphodiinae. The Cetoniinae was sister to the Dynastinae + Rutelinae clade. The Melolonthinae was a non-monophyletic group. The removal of fast-evolving sites from nucleotide dataset using a pattern sorting method (OV-sorting) supported the family Scarabaeidae as a monophyletic group. At the tribe level, the Onthophagini was non-monophyletic with respect to Oniticellini. Ateuchini was sister to a large clade comprising the tribes Onthophagini, Oniticellini and Onitini. Eurysternini was a sister group of the Phanaeini + Ateuchini clade.}, } @article {pmid36508337, year = {2022}, author = {Xu, R and Martelossi, J and Smits, M and Iannello, M and Peruzza, L and Babbucci, M and Milan, M and Dunham, JP and Breton, S and Milani, L and Nuzhdin, SV and Bargelloni, L and Passamonti, M and Ghiselli, F}, title = {Multi-tissue RNA-Seq analysis and long-read-based genome assembly reveal complex sex-specific gene regulation and molecular evolution in the Manila clam.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evac171}, pmid = {36508337}, issn = {1759-6653}, abstract = {The molecular factors and gene regulation involved in sex determination and gonad differentiation in bivalve molluscs are unknown. It has been suggested that doubly uniparental inheritance (DUI) of mitochondria may be involved in these processes in species such as the ubiquitous and commercially relevant Manila clam, Ruditapes philippinarum. We present the first long-read-based de novo genome assembly of a Manila clam, and a RNA-Seq multi-tissue analysis of 15 females and 15 males. The highly contiguous genome assembly was used as reference to investigate gene expression, alternative splicing, sequence evolution, tissue-specific co-expression networks, and sexual contrasting SNPs. Differential expression and differential splicing analyses revealed sex-specific transcriptional regulation in gonads, but not in somatic tissues. Co-expression networks revealed complex gene regulation in gonads, and genes in gonad-associated modules showed high tissue specificity. However, male gonad-associated modules showed contrasting patterns of sequence evolution and tissue specificity. One gene set was related to the structural organization of male gametes and presented slow sequence evolution but high pleiotropy, while another gene set was enriched in reproduction-related processes and characterized by fast sequence evolution and tissue specificity. Sexual contrasting SNPs were found in genes overrepresented in mitochondrial related functions, providing new candidates for investigating the relationship between mitochondria and sex in DUI species. Together, these results increase our understanding of the role of differential expression, differential splicing, and sequence evolution of sex-specific genes in an understudied taxon. We also provide resourceful genomic data for studies regarding sex diagnosis and breeding in bivalves.}, } @article {pmid36502540, year = {2022}, author = {Alsaad, RKA}, title = {Past, present and future of Trichomonas vaginalis: a review study.}, journal = {Annals of parasitology}, volume = {68}, number = {3}, pages = {409-419}, doi = {10.17420/ap6803.447}, pmid = {36502540}, issn = {2299-0631}, mesh = {Male ; Female ; Humans ; *Trichomonas vaginalis/genetics ; *Trichomonas Vaginitis/diagnosis/epidemiology/parasitology ; *Trichomonas Infections/epidemiology ; Metronidazole ; Prevalence ; }, abstract = {Trichomonas vaginalis (TV) is the most common non-viral sexually transmitted infection (STI) microaerophilic protist parasite, which is the causative agent of trichomonosis. Globally, the estimated annual incidence is more than 270 million cases. It is correlated for several health problems including pelvic inflammatory disease (PID), pregnancy miscarriages, cervical carcinoma, prostatitis, prostatic adenocarcinomas, infertility, and the acquisition of human immunodeficiency virus (HIV). Most individuals infected with TV are asymptomatic. Metronidazole (MTZ) has been the treatment of choice for women. Currently, there is no effective vaccine against this pathogen despite efforts at vaccine development. Different socio-economic, demographic, behavioral, and biological factors are associated with the disease. Apart from its role as a pathogenic agent of diseases, it is also a fascinating organism with a surprisingly large genome for a parasite, i.e. larger than 160 Mb, and physiology adapted to its microaerophilic lifestyle. Particularly, the hydrogenosome, a mitochondria-derived organelle that releases hydrogen, attracted much interest in the last decades and rendered TV a model organism for eukaryotic evolution. According to the high prevalence and health consequences associated with TV, there is a requirement for improved screening programs in Iraq. The early diagnosis of asymptomatic diseases and effective treatment regimens are mandatory. Despite being highly prevalent of trichomonosis in the world, there is no review research published that solely focuses on T. vaginalis infections in Iraq.}, } @article {pmid36501134, year = {2022}, author = {Żmijewski, MA}, title = {Nongenomic Activities of Vitamin D.}, journal = {Nutrients}, volume = {14}, number = {23}, pages = {}, pmid = {36501134}, issn = {2072-6643}, mesh = {*Receptors, Calcitriol/genetics ; *Vitamin D/pharmacology/metabolism ; Calcium/metabolism ; Ultraviolet Rays ; Hedgehog Proteins ; Calcitriol/metabolism ; Vitamins ; }, abstract = {Vitamin D shows a variety of pleiotropic activities which cannot be fully explained by the stimulation of classic pathway- and vitamin D receptor (VDR)-dependent transcriptional modulation. Thus, existence of rapid and nongenomic responses to vitamin D was suggested. An active form of vitamin D (calcitriol, 1,25(OH)2D3) is an essential regulator of calcium-phosphate homeostasis, and this process is tightly regulated by VDR genomic activity. However, it seems that early in evolution, the production of secosteroids (vitamin-D-like steroids) and their subsequent photodegradation served as a protective mechanism against ultraviolet radiation and oxidative stress. Consequently, direct cell-protective activities of vitamin D were proven. Furthermore, calcitriol triggers rapid calcium influx through epithelia and its uptake by a variety of cells. Subsequently, protein disulfide-isomerase A3 (PDIA3) was described as a membrane vitamin D receptor responsible for rapid nongenomic responses. Vitamin D was also found to stimulate a release of secondary massagers and modulate several intracellular processes-including cell cycle, proliferation, or immune responses-through wingless (WNT), sonic hedgehog (SSH), STAT1-3, or NF-kappaB pathways. Megalin and its coreceptor, cubilin, facilitate the import of vitamin D complex with vitamin-D-binding protein (DBP), and its involvement in rapid membrane responses was suggested. Vitamin D also directly and indirectly influences mitochondrial function, including fusion-fission, energy production, mitochondrial membrane potential, activity of ion channels, and apoptosis. Although mechanisms of the nongenomic responses to vitamin D are still not fully understood, in this review, their impact on physiology, pathology, and potential clinical applications will be discussed.}, } @article {pmid36498828, year = {2022}, author = {Ge, Q and Peng, P and Cheng, M and Meng, Y and Cao, Y and Zhang, S and Long, Y and Li, G and Kang, G}, title = {Genome-Wide Identification and Analysis of FKBP Gene Family in Wheat (Triticum asetivum).}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36498828}, issn = {1422-0067}, mesh = {*Triticum/metabolism ; Genome, Plant ; Phylogeny ; Gene Expression Regulation, Plant ; Tacrolimus Binding Proteins/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Stress, Physiological/genetics ; *Arabidopsis/genetics ; Multigene Family ; }, abstract = {FK506-binding protein (FKBP) genes have been found to play vital roles in plant development and abiotic stress responses. However, limited information is available about this gene family in wheat (Triticum aestivum L.). In this study, a total of 64 FKBP genes were identified in wheat via a genome-wide analysis involving a homologous search of the latest wheat genome data, which was unevenly distributed in 21 chromosomes, encoded 152 to 649 amino acids with molecular weights ranging from 16 kDa to 72 kDa, and was localized in the chloroplast, cytoplasm, nucleus, mitochondria, peroxisome and endoplasmic reticulum. Based on sequence alignment and phylogenetic analysis, 64 TaFKBPs were divided into four different groups or subfamilies, providing evidence of an evolutionary relationship with Aegilops tauschii, Brachypodium distachyon, Triticum dicoccoides, Arabidopsis thaliana and Oryza sativa. Hormone-related, abiotic stress-related and development-related cis-elements were preferentially presented in promoters of TaFKBPs. The expression levels of TaFKBP genes were investigated using transcriptome data from the WheatExp database, which exhibited tissue-specific expression patterns. Moreover, TaFKBPs responded to drought and heat stress, and nine of them were randomly selected for validation by qRT-PCR. Yeast cells expressing TaFKBP19-2B-2 or TaFKBP18-6B showed increased influence on drought stress, indicating their negative roles in drought tolerance. Collectively, our results provide valuable information about the FKBP gene family in wheat and contribute to further characterization of FKBPs during plant development and abiotic stress responses, especially in drought stress.}, } @article {pmid36497015, year = {2022}, author = {Kozhukhar, N and Alexeyev, MF}, title = {TFAM's Contributions to mtDNA Replication and OXPHOS Biogenesis Are Genetically Separable.}, journal = {Cells}, volume = {11}, number = {23}, pages = {}, pmid = {36497015}, issn = {2073-4409}, mesh = {Animals ; Humans ; Phylogeny ; *Chickens/genetics/metabolism ; *DNA Replication/genetics ; DNA, Mitochondrial/genetics/metabolism ; Mitochondria/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Transcription Factors/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; }, abstract = {The ability of animal orthologs of human mitochondrial transcription factor A (hTFAM) to support the replication of human mitochondrial DNA (hmtDNA) does not follow a simple pattern of phylogenetic closeness or sequence similarity. In particular, TFAM from chickens (Gallus gallus, chTFAM), unlike TFAM from the "living fossil" fish coelacanth (Latimeria chalumnae), cannot support hmtDNA replication. Here, we implemented the recently developed GeneSwap approach for reverse genetic analysis of chTFAM to obtain insights into this apparent contradiction. By implementing limited "humanization" of chTFAM focused either on amino acid residues that make DNA contacts, or the ones with significant variances in side chains, we isolated two variants, Ch13 and Ch22. The former has a low mtDNA copy number (mtCN) but robust respiration. The converse is true of Ch22. Ch13 and Ch22 complement each other's deficiencies. Opposite directionalities of changes in mtCN and respiration were also observed in cells expressing frog TFAM. This led us to conclude that TFAM's contributions to mtDNA replication and respiratory chain biogenesis are genetically separable. We also present evidence that TFAM residues that make DNA contacts play the leading role in mtDNA replication. Finally, we present evidence for a novel mode of regulation of the respiratory chain biogenesis by regulating the supply of rRNA subunits.}, } @article {pmid36473440, year = {2022}, author = {Leger, MM and Stairs, C}, title = {Eukaryotic evolution: Spatial proteomics sheds light on mitochondrial reduction.}, journal = {Current biology : CB}, volume = {32}, number = {23}, pages = {R1308-R1311}, doi = {10.1016/j.cub.2022.10.039}, pmid = {36473440}, issn = {1879-0445}, mesh = {*Eukaryota ; *Proteomics ; }, abstract = {Multi-organelle spatial proteomics has revolutionized animal cell biology, but its use in protists has so far been limited. A new study delivers the first such proteome of a free-living protist, uncovering a previously overlooked function of highly reduced mitochondria.}, } @article {pmid36472108, year = {2022}, author = {Cahill, MA}, title = {Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {27}, number = {11}, pages = {317}, doi = {10.31083/j.fbl2711317}, pmid = {36472108}, issn = {2768-6698}, mesh = {Animals ; Humans ; *Eukaryota ; *Proteomics ; Epigenesis, Genetic ; Receptors, Progesterone/metabolism ; Glycolysis ; Heme/metabolism ; Mammals/metabolism ; Membrane Proteins/genetics/metabolism ; }, abstract = {The title usage of Unde venisti 'from where have you come' is from a now dead language (Latin) that foundationally influenced modern English (not the major influence, but an essential formative one). This is an apt analogy for how both the ancient eukaryotic and eumetazoan functions of PGRMC proteins (PGRMC1 and PGRMC2 in mammals) probably influence modern human biology: via a formative trajectory from an evolutionarily foundational fulcrum. There is an arguable probability, although not a certainty, that PGRMC-like proteins were involved in eukaryogenesis. If so, then the proto-eukaryotic ancestral protein is modelled as having initiated the oxygen-induced and CYP450 (Cytochrome P450)-mediated synthesis of sterols in the endoplasmic reticulum to regulate proto-mitochondrial activity and heme homeostasis, as well as having enabled sterol transport between endoplasmic reticulum (ER) and mitochondria membranes involving the actin cytoskeleton, transport of heme from mitochondria, and possibly the regulation/origins of mitosis/meiosis. Later, during animal evolution, the last eumetazoan common ancestor (LEUMCA) acquired PGRMC phosphorylated tyrosines coincidentally with the gastrulation organizer, Netrin/deleted in colorectal carcinoma (DCC) signaling, muscle fibers, synapsed neurons, and neural recovery via a sleep-like process. Modern PGRMC proteins regulate multiple functions, including CYP450-mediated steroidogenesis, membrane trafficking, heme homeostasis, glycolysis/Warburg effect, fatty acid metabolism, mitochondrial regulation, and genomic CpG epigenetic regulation of gene expression. The latter imposes the system of differentiation status-sensitive cell-type specific proteomic complements in multi-tissued descendants of the LEUMCA. This paper attempts to trace PGRMC functions through time, proposing that key functions were involved in early eukaryotes, and were later added upon in the LEUMCA. An accompanying paper considers the implications of this awareness for human health and disease.}, } @article {pmid36450825, year = {2022}, author = {Missiroli, S and Perrone, M and Gafà, R and Nicoli, F and Bonora, M and Morciano, G and Boncompagni, C and Marchi, S and Lebiedzinska-Arciszewska, M and Vezzani, B and Lanza, G and Kricek, F and Borghi, A and Fiorica, F and Ito, K and Wieckowski, MR and Di Virgilio, F and Abelli, L and Pinton, P and Giorgi, C}, title = {PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment.}, journal = {Cell death and differentiation}, volume = {}, number = {}, pages = {1-13}, pmid = {36450825}, issn = {1476-5403}, support = {R01 DK098263/DK/NIDDK NIH HHS/United States ; R01 HL148852/HL/NHLBI NIH HHS/United States ; R01 DK115577/DK/NIDDK NIH HHS/United States ; }, abstract = {Uncontrolled inflammatory response arising from the tumor microenvironment (TME) significantly contributes to cancer progression, prompting an investigation and careful evaluation of counter-regulatory mechanisms. We identified a trimeric complex at the mitochondria-associated membranes (MAMs), in which the purinergic P2X7 receptor - NLRP3 inflammasome liaison is fine-tuned by the tumor suppressor PML. PML downregulation drives an exacerbated immune response due to a loss of P2X7R-NLRP3 restraint that boosts tumor growth. PML mislocalization from MAMs elicits an uncontrolled NLRP3 activation, and consequent cytokines blast fueling cancer and worsening the tumor prognosis in different human cancers. New mechanistic insights are provided for the PML-P2X7R-NLRP3 axis to govern the TME in human carcinogenesis, fostering new targeted therapeutic approaches.}, } @article {pmid36442091, year = {2022}, author = {Insalata, F and Hoitzing, H and Aryaman, J and Jones, NS}, title = {Stochastic survival of the densest and mitochondrial DNA clonal expansion in aging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {49}, pages = {e2122073119}, doi = {10.1073/pnas.2122073119}, pmid = {36442091}, issn = {1091-6490}, mesh = {*DNA, Mitochondrial/genetics ; *Mitochondria ; Cellular Senescence/genetics ; Muscle Fibers, Skeletal ; }, abstract = {The expansion of mitochondrial DNA molecules with deletions has been associated with aging, particularly in skeletal muscle fibers; its mechanism has remained unclear for three decades. Previous accounts have assigned a replicative advantage (RA) to mitochondrial DNA containing deletion mutations, but there is also evidence that cells can selectively remove defective mitochondrial DNA. Here we present a spatial model that, without an RA, but instead through a combination of enhanced density for mutants and noise, produces a wave of expanding mutations with speeds consistent with experimental data. A standard model based on RA yields waves that are too fast. We provide a formula that predicts that wave speed drops with copy number, consonant with experimental data. Crucially, our model yields traveling waves of mutants even if mutants are preferentially eliminated. Additionally, we predict that mutant loads observed in single-cell experiments can be produced by de novo mutation rates that are drastically lower than previously thought for neutral models. Given this exemplar of how spatial structure (multiple linked mtDNA populations), noise, and density affect muscle cell aging, we introduce the mechanism of stochastic survival of the densest (SSD), an alternative to RA, that may underpin other evolutionary phenomena.}, } @article {pmid36430970, year = {2022}, author = {Pożoga, M and Armbruster, L and Wirtz, M}, title = {From Nucleus to Membrane: A Subcellular Map of the N-Acetylation Machinery in Plants.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430970}, issn = {1422-0067}, mesh = {Humans ; Acetylation ; *Saccharomyces cerevisiae ; *Protein Processing, Post-Translational ; Plants/metabolism ; }, abstract = {N-terminal acetylation (NTA) is an ancient protein modification conserved throughout all domains of life. N-terminally acetylated proteins are present in the cytosol, the nucleus, the plastids, mitochondria and the plasma membrane of plants. The frequency of NTA differs greatly between these subcellular compartments. While up to 80% of cytosolic and 20-30% of plastidic proteins are subject to NTA, NTA of mitochondrial proteins is rare. NTA alters key characteristics of proteins such as their three-dimensional structure, binding properties and lifetime. Since the majority of proteins is acetylated by five ribosome-bound N-terminal acetyltransferases (Nats) in yeast and humans, NTA was long perceived as an exclusively co-translational process in eukaryotes. The recent characterization of post-translationally acting plant Nats, which localize to the plasma membrane and the plastids, has challenged this view. Moreover, findings in humans, yeast, green algae and higher plants uncover differences in the cytosolic Nat machinery of photosynthetic and non-photosynthetic eukaryotes. These distinctive features of the plant Nat machinery might constitute adaptations to the sessile lifestyle of plants. This review sheds light on the unique role of plant N-acetyltransferases in development and stress responses as well as their evolution-driven adaptation to function in different cellular compartments.}, } @article {pmid36427759, year = {2022}, author = {Munro, D and Rodríguez, E and Blier, PU}, title = {The longest-lived metazoan, Arctica islandica, exhibits high mitochondrial H2O2 removal capacities.}, journal = {Mitochondrion}, volume = {68}, number = {}, pages = {81-86}, doi = {10.1016/j.mito.2022.11.005}, pmid = {36427759}, issn = {1872-8278}, abstract = {A greater capacity of endogenous matrix antioxidants has recently been hypothesized to characterize mitochondria of long-lived species, curbing bursts of reactive oxygen species (ROS) generated in this organelle. Evidence for this has been obtained from studies comparing the long-lived naked mole rat to laboratory mice. We tested this hypothesis by comparing the longest-lived metazoan, the marine bivalve Arctica islandica (MLSP = 507 y), with shorter-lived and evolutionarily related species. We used a recently developed fluorescent technique to assess mantle and gill tissue mitochondria's capacity to consume hydrogen peroxide (H2O2) in multiple physiological states ex vivo. Depending on the type of respiratory substrate provided, mitochondria of Arctica islandica could consume between 3 and 14 times more H2O2 than shorter-lived species. These findings support the contention that a greater capacity for the elimination of ROS characterizes long-lived species, a novel property of mitochondria thus far demonstrated in two key biogerontological models from distant evolutionary lineages.}, } @article {pmid36421831, year = {2022}, author = {Tang, Y and Huo, Z and Liu, Y and Wang, Y and Zuo, L and Fang, L and Zhao, W and Tan, Y and Yan, X}, title = {Full Mitochondrial Genomes Reveal Species Differences between the Venerid Clams Ruditapes philippinarum and R. variegatus.}, journal = {Genes}, volume = {13}, number = {11}, pages = {}, pmid = {36421831}, issn = {2073-4425}, mesh = {Animals ; *Genome, Mitochondrial/genetics ; Phylogeny ; Species Specificity ; NADH Dehydrogenase ; *Bivalvia/genetics ; }, abstract = {In natural sea areas along the coast of China, venerid clams Ruditapes philippinarum and R. variegatus exhibit similar adult shell forms and are especially difficult to distinguish as spat and juveniles. This study used comparative mitochondrial genome analysis to reveal differences between these species. The results showed that: (1) the mitochondrial genomes of R. philippinarum and R. variegatus share a large number of similar gene clusters arranged in consistent order, yet they also display noncommon genes, with both gene rearrangements and random losses found; (2) the 13 protein-coding genes in R. philippinarum as well as two-fold and four-fold degenerate sites in R. variegatus have an evident AT bias; (3) the Ka/Ks ratio of the mitochondrial ATP8 gene was significantly higher in R. philippinarum than in R. variegatus, and an analysis of selection pressure revealed that the mitochondrial NADH dehydrogenase subunit 2 gene and NADH dehydrogenase subunit 6 gene of R. variegatus were under great selective pressure during its evolution; and finally, (4) the two species clustered into one branch on a phylogenetic tree, further affirming their phylogenetic closeness. Based on these results, we speculate that the species differences between R. variegatus and R. philippinarum are largely attributable to adaptive evolution to the environment. The present findings provide a reference for the development of germplasm identification.}, } @article {pmid36421825, year = {2022}, author = {Kyrgiafini, MA and Giannoulis, T and Moutou, KA and Mamuris, Z}, title = {Investigating the Impact of a Curse: Diseases, Population Isolation, Evolution and the Mother's Curse.}, journal = {Genes}, volume = {13}, number = {11}, pages = {}, pmid = {36421825}, issn = {2073-4425}, mesh = {Male ; Female ; Humans ; *Mothers ; DNA, Mitochondrial/genetics ; Maternal Inheritance/genetics ; *Genome, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {The mitochondrion was characterized for years as the energy factory of the cell, but now its role in many more cellular processes is recognized. The mitochondrion and mitochondrial DNA (mtDNA) also possess a set of distinct properties, including maternal inheritance, that creates the Mother's Curse phenomenon. As mtDNA is inherited from females to all offspring, mutations that are harmful to males tend to accumulate more easily. The Mother's Curse is associated with various diseases, and has a significant effect on males, in many cases even affecting their reproductive ability. Sometimes, it even leads to reproductive isolation, as in crosses between different populations, the mitochondrial genome cannot cooperate effectively with the nuclear one resulting in a mito-nuclear incompatibility and reduce the fitness of the hybrids. This phenomenon is observed both in the laboratory and in natural populations, and have the potential to influence their evolution and speciation. Therefore, it turns out that the study of mitochondria is an exciting field that finds many applications, including pest control, and it can shed light on the molecular mechanism of several diseases, improving successful diagnosis and therapeutics. Finally, mito-nuclear co-adaptation, paternal leakage, and kin selection are some mechanisms that can mitigate the impact of the Mother's Curse.}, } @article {pmid36421375, year = {2022}, author = {Ding, H and Bi, D and Zhang, S and Han, S and Ye, Y and Yi, R and Yang, J and Liu, B and Wu, L and Zhuo, R and Kan, X}, title = {The Mitogenome of Sedum plumbizincicola (Crassulaceae): Insights into RNA Editing, Lateral Gene Transfer, and Phylogenetic Implications.}, journal = {Biology}, volume = {11}, number = {11}, pages = {}, pmid = {36421375}, issn = {2079-7737}, abstract = {As the largest family within the order Saxifragales, Crassulaceae contains about 34 genera with 1400 species. Mitochondria play a critical role in cellular energy production. Since the first land plant mitogenome was reported in Arabidopsis, more than 400 mitogenomic sequences have been deposited in a public database. However, no entire mitogenome data have been available for species of Crassulaceae to date. To better understand the evolutionary history of the organelles of Crassulaceae, we sequenced and performed comprehensive analyses on the mitogenome of Sedum plumbizincicola. The master mitogenomic circle is 212,159 bp in length, including 31 protein-coding genes (PCGs), 14 tRNA genes, and 3 rRNA genes. We further identified totally 508 RNA editing sites in PCGs, and demonstrated that the second codon positions of mitochondrial genes are most prone to RNA editing events. Notably, by neutrality plot analyses, we observed that the mitochondrial RNA editing events have large effects on the driving forces of plant evolution. Additionally, 4 MTPTs and 686 NUMTs were detected in the mitochondrial and nuclear genomes of S. plumbizincicola, respectively. Additionally, we conducted further analyses on gene transfer, secondary structures of mitochondrial RNAs, and phylogenetic implications. Therefore, the findings presented here will be helpful for future investigations on plant mitogenomes.}, } @article {pmid36417880, year = {2022}, author = {Aman, Y and Erinjeri, AP and Tataridas-Pallas, N and Williams, R and Wellman, R and Chapman, H and Labbadia, J}, title = {Loss of MTCH-1 suppresses age-related proteostasis collapse through the inhibition of programmed cell death factors.}, journal = {Cell reports}, volume = {41}, number = {8}, pages = {111690}, doi = {10.1016/j.celrep.2022.111690}, pmid = {36417880}, issn = {2211-1247}, support = {BB/P005535/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Proteostasis/physiology ; *Proteome/metabolism ; Protein Folding ; Caenorhabditis elegans/metabolism ; Apoptosis ; }, abstract = {The age-related loss of protein homeostasis (proteostasis) is at the heart of numerous neurodegenerative diseases. Therefore, finding ways to preserve proteome integrity in aged cells may be a powerful way to promote long-term health. Here, we show that reducing the activity of a highly conserved mitochondrial outer membrane protein, MTCH-1/MTCH2, suppresses age-related proteostasis collapse in Caenorhabditis elegans without disrupting development, growth, or reproduction. Loss of MTCH-1 does not influence proteostasis capacity in aged tissues through previously described pathways but instead operates by reducing CED-4 levels. This results in the sequestration of HSP-90 by inactive CED-3, which in turn leads to an increase in HSF-1 activity, transcriptional remodeling of the proteostasis network, and maintenance of proteostasis capacity with age. Together, our findings reveal a role for programmed cell death factors in determining proteome health and suggest that inhibiting MTCH-1 activity in adulthood may safeguard the aging proteome and suppress age-related diseases.}, } @article {pmid36414480, year = {2023}, author = {Sahayasheela, VJ and Yu, Z and Hidaka, T and Pandian, GN and Sugiyama, H}, title = {Mitochondria and G-quadruplex evolution: an intertwined relationship.}, journal = {Trends in genetics : TIG}, volume = {39}, number = {1}, pages = {15-30}, pmid = {36414480}, issn = {0168-9525}, mesh = {Humans ; *G-Quadruplexes ; Mitochondria/genetics ; }, abstract = {G-quadruplexes (G4s) are non-canonical structures formed in guanine (G)-rich sequences through stacked G tetrads by Hoogsteen hydrogen bonding. Several studies have demonstrated the existence of G4s in the genome of various organisms, including humans, and have proposed that G4s have a regulatory role in various cellular functions. However, little is known regarding the dissemination of G4s in mitochondria. In this review, we report the observation that the number of potential G4-forming sequences in the mitochondrial genome increases with the evolutionary complexity of different species, suggesting that G4s have a beneficial role in higher-order organisms. We also discuss the possible function of G4s in mitochondrial (mt)DNA and long noncoding (lnc)RNA and their role in various biological processes.}, } @article {pmid36413915, year = {2023}, author = {Guette-Marquet, S and Roques, C and Bergel, A}, title = {Direct electrochemical detection of trans-plasma membrane electron transfer: A possible alternative pathway for cell respiration.}, journal = {Biosensors & bioelectronics}, volume = {220}, number = {}, pages = {114896}, doi = {10.1016/j.bios.2022.114896}, pmid = {36413915}, issn = {1873-4235}, mesh = {Chlorocebus aethiops ; Animals ; *Electrons ; Vero Cells ; *Biosensing Techniques ; Cell Respiration ; Cell Membrane ; Carbon ; }, abstract = {An electrochemical protocol was designed to enable Vero cells to transfer electrons to an electrode without any added redox mediator. The cells were cultured on the surface of electrodes polarized at the optimal potential of 400 mV/silver pseudo-reference. Gold, carbon, and CNT-coated carbon electrodes displayed similar current record patterns. Extracellular electron transfer was sustained for several days. Its intensity, up to 1.5 pA.cell[-1], was in the range of the electron flows implemented by cell respiration. A large fraction of the current vanished as soon as anoxic conditions were established, which suggests a mitochondrial origin for a large proportion of the electrons. The current records always showed a two-phase pattern. The occurrence of the two phases was not due to an evolution of the cell mat structure, which was fully established during the first day of polarization and did not change significantly thereafter. Increasing the cell seeding density decreased the maximum current reached during the first phase and the duration of the phase. These observations put together lead us to propose a model, in which only the cells adhered on the electrode surface produced current by metabolizing glutamine during the first phase. The possible role of this extracellular electron transfer as an alternative cell respiration pathway is discussed. The key roles it could play in regulating pH and pO2 gradients are considered, specifically to explain the pH gradient reversal observed in cancer cells. These pioneering results pave the way for electrochemical sensors to directly address cellular metabolic pathways.}, } @article {pmid36403966, year = {2022}, author = {Maciszewski, K and Fells, A and Karnkowska, A}, title = {Challenging the Importance of Plastid Genome Structure Conservation: New Insights From Euglenophytes.}, journal = {Molecular biology and evolution}, volume = {39}, number = {12}, pages = {}, pmid = {36403966}, issn = {1537-1719}, mesh = {*Social Group ; *Genome, Plastid ; }, abstract = {Plastids, similar to mitochondria, are organelles of endosymbiotic origin, which retained their vestigial genomes (ptDNA). Their unique architecture, commonly referred to as the quadripartite (four-part) structure, is considered to be strictly conserved; however, the bulk of our knowledge on their variability and evolutionary transformations comes from studies of the primary plastids of green algae and land plants. To broaden our perspective, we obtained seven new ptDNA sequences from freshwater species of photosynthetic euglenids-a group that obtained secondary plastids, known to have dynamically evolving genome structure, via endosymbiosis with a green alga. Our analyses have demonstrated that the evolutionary history of euglenid plastid genome structure is exceptionally convoluted, with a patchy distribution of inverted ribosomal operon (rDNA) repeats, as well as several independent acquisitions of tandemly repeated rDNA copies. Moreover, we have shown that inverted repeats in euglenid ptDNA do not share their genome-stabilizing property documented in chlorophytes. We hypothesize that the degeneration of the quadripartite structure of euglenid plastid genomes is connected to the group II intron expansion. These findings challenge the current global paradigms of plastid genome architecture evolution and underscore the often-underestimated divergence between the functionality of shared traits in primary and complex plastid organelles.}, } @article {pmid36397290, year = {2022}, author = {Mallard, J and Hucteau, E and Schott, R and Trensz, P and Pflumio, C and Kalish-Weindling, M and Favret, F and Pivot, X and Hureau, TJ and Pagano, AF}, title = {Early skeletal muscle deconditioning and reduced exercise capacity during (neo)adjuvant chemotherapy in patients with breast cancer.}, journal = {Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/cncr.34533}, pmid = {36397290}, issn = {1097-0142}, abstract = {BACKGROUND: Fatigue is a hallmark of breast cancer and is associated with skeletal muscle deconditioning. If cancer-related fatigue occurs early during chemotherapy (CT), the development of skeletal muscle deconditioning and its effect on exercise capacity remain unclear. The aim of this study was to investigate the evolution of skeletal muscle deconditioning and exercise capacity in patients with early-stage breast cancer during CT.

METHODS: Patients with breast cancer had a visit before undergoing CT, at 8 weeks, and at the end of chemotherapy (post-CT). Body composition was determined through bioelectrical impedance analysis. Knee extensor, handgrip muscle force and fatigue was quantified by performing maximal voluntary isometric contractions and exercise capacity using the 6-min walking test. Questionnaires were also administered to evaluate quality of life, cancer-related fatigue, and physical activity level.

RESULTS: Among the 100 patients, reductions were found in muscle mass (-2.3%, p = .002), exercise capacity (-6.7%, p < .001), and knee extensor force (-4.9%, p < .001) post-CT, which occurred within the first 8 weeks of treatment with no further decrease thereafter. If muscle fatigue did not change, handgrip muscle force decreased post-CT only (-2.5%, p = .001), and exercise capacity continued to decrease between 8 weeks and post-CT (-4.6%, p < .001). Quality of life and cancer-related fatigue were impaired after 8 weeks (p < .001) and remained stable thereafter, whereas the physical activity level remained stable during chemotherapy.

CONCLUSIONS: Similar to cancer-related fatigue, skeletal muscle deconditioning and reduced exercise capacity occurred early during breast cancer CT. Thus, it appears essential to prevent these alterations through exercise training implemented during CT.}, } @article {pmid36386853, year = {2022}, author = {Radzvilavicius, AL and Johnston, IG}, title = {Organelle bottlenecks facilitate evolvability by traversing heteroplasmic fitness valleys.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {974472}, pmid = {36386853}, issn = {1664-8021}, abstract = {Bioenergetic organelles-mitochondria and plastids-retain their own genomes (mtDNA and ptDNA), and these organelle DNA (oDNA) molecules are vital for eukaryotic life. Like all genomes, oDNA must be able to evolve to suit new environmental challenges. However, mixed oDNA populations in cells can challenge cellular bioenergetics, providing a penalty to the appearance and adaptation of new mutations. Here we show that organelle "bottlenecks," mechanisms increasing cell-to-cell oDNA variability during development, can overcome this mixture penalty and facilitate the adaptation of beneficial mutations. We show that oDNA heteroplasmy and bottlenecks naturally emerge in evolutionary simulations subjected to fluctuating environments, demonstrating that this evolvability is itself evolvable. Usually thought of as a mechanism to clear damaging mutations, organelle bottlenecks therefore also resolve the tension between intracellular selection for pure cellular oDNA populations and the "bet-hedging" need for evolvability and adaptation to new environments. This general theory suggests a reason for the maintenance of organelle heteroplasmy in cells, and may explain some of the observed diversity in organelle maintenance and inheritance across taxa.}, } @article {pmid36382523, year = {2022}, author = {Watson, ET and Flanagan, BA and Pascar, JA and Edmands, S}, title = {Mitochondrial effects on fertility and longevity in Tigriopus californicus contradict predictions of the mother's curse hypothesis.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1987}, pages = {20221211}, pmid = {36382523}, issn = {1471-2954}, mesh = {Female ; Animals ; *Longevity ; Mitochondria/genetics ; Maternal Inheritance ; Fertility ; *Genome, Mitochondrial ; DNA, Mitochondrial/genetics ; }, abstract = {Strict maternal inheritance of mitochondria favours the evolutionary accumulation of sex-biased fitness effects, as mitochondrial evolution occurs exclusively in female lineages. The 'mother's curse' hypothesis proposes that male-harming mutations should accumulate in mitochondrial genomes when they have neutral or beneficial effects on female fitness. Rigorous empirical tests have largely focused on Drosophila, where support for the predictions of mother's curse has been mixed. We investigated the impact of mother's curse mutations in Tigriopus californicus, a minute crustacean. Using non-recombinant backcrosses, we introgressed four divergent mitochondrial haplotypes into two nuclear backgrounds and recorded measures of fertility and longevity. We found that the phenotypic effects of mitochondrial mutations were context dependent, being influenced by the nuclear background in which they were expressed, as well as the sex of the individual and rearing temperature. Mitochondrial haplotype effects were greater for fertility than longevity, and temperature effects were greater for longevity. However, in opposition to mother's curse expectations, females had higher mitochondrial genetic variance than males for fertility and longevity, little evidence of sexual antagonism favouring females was found, and the impacts of mitonuclear mismatch harmed females but not males. Together, this indicates that selection on mitochondrial variation has not resulted in the accumulation of male mutation load in Tigriopus californicus.}, } @article {pmid36373631, year = {2023}, author = {Mencía, M}, title = {Acid digestion and symbiont: Proton sharing at the origin of mitochondriogenesis?: Proton production by a symbiotic bacterium may have been the origin of two hallmark eukaryotic features, acid digestion and mitochondria: Proton production by a symbiotic bacterium may have been the origin of two hallmark eukaryotic features, acid digestion and mitochondria.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {1}, pages = {e2200136}, doi = {10.1002/bies.202200136}, pmid = {36373631}, issn = {1521-1878}, mesh = {*Protons ; Phylogeny ; *Eukaryota ; Symbiosis ; Bacteria ; Mitochondria ; Digestion ; Biological Evolution ; }, abstract = {The initial relationships between organisms leading to endosymbiosis and the first eukaryote are currently a topic of hot debate. Here, I present a theory that offers a gradual scenario in which the origins of phagocytosis and mitochondria are intertwined in such a way that the evolution of one would not be possible without the other. In this scenario, the premitochondrial bacterial symbiont became initially associated with a protophagocytic host on the basis of cooperation to kill prey with symbiont-produced toxins and reactive oxygen species (ROS). Subsequently, the cooperation was focused on the digestion stage, through the acidification of the protophagocytic cavities via exportation of protons produced by the aerobic respiration of the symbiont. The host gained an improved phagocytic capacity and the symbiont received organic compounds from prey. As the host gradually lost its membrane energetics to develop lysosomal digestion, respiration was centralized in the premitochondrial symbiont for energy production for the consortium.}, } @article {pmid36362255, year = {2022}, author = {Zhao, W and Bu, X and Zou, H and Li, W and Wu, S and Li, M and Wang, G}, title = {The Genome of the Mitochondrion-Related Organelle in Cepedea longa, a Large Endosymbiotic Opalinid Inhabiting the Recta of Frogs.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362255}, issn = {1422-0067}, mesh = {Animals ; Phylogeny ; *Anura/genetics ; *Stramenopiles/genetics ; Organelles/metabolism ; Mitochondria/genetics ; }, abstract = {Mitochondrion-related organelles (MROs) are loosely defined as degenerated mitochondria in anaerobic and microaerophilic lineages. Opalinids are commonly regarded as commensals in the guts of cold-blooded amphibians. It may represent an intermediate adaptation stage between the conventional aerobic mitochondria and derived anaerobic MROs. In the present study, we sequenced and analyzed the MRO genome of Cepedea longa. It has a linear MRO genome with large inverted repeat gene regions at both ends. Compared to Blastocystis and Proteromonas lacertae, the MRO genome of C. longa has a higher G + C content and repeat sequences near the central region. Although three Opalinata species have different morphological characteristics, phylogenetic analyses based on eight concatenated nad genes indicate that they are close relatives. The phylogenetic analysis showed that C. longa clustered with P. lacertae with strong support. The 18S rRNA gene-based phylogeny resolved the Opalinea clade as a sister clade to Karotomorpha, which then further grouped with Proteromonas. The paraphyly of Proteromonadea needs to be verified due to the lack of MRO genomes for key species, such as Karotomorpha, Opalina and Protoopalina. Besides, our dataset and analyses offered slight support for the paraphyly of Bigyra.}, } @article {pmid36361939, year = {2022}, author = {Alves, R and Pazos-Gil, M and Medina-Carbonero, M and Sanz-Alcázar, A and Delaspre, F and Tamarit, J}, title = {Evolution of an Iron-Detoxifying Protein: Eukaryotic and Rickettsia Frataxins Contain a Conserved Site Which Is Not Present in Their Bacterial Homologues.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36361939}, issn = {1422-0067}, mesh = {Humans ; Bacterial Proteins/chemistry/metabolism ; Escherichia coli/metabolism ; Escherichia coli Proteins/genetics ; Eukaryota/metabolism ; Friedreich Ataxia/genetics/metabolism ; Iron/metabolism ; *Iron-Binding Proteins/chemistry/metabolism ; *Neurodegenerative Diseases ; *Rickettsia/metabolism ; Tyrosine/metabolism ; Mitochondria/metabolism/microbiology ; }, abstract = {Friedreich's ataxia is a neurodegenerative disease caused by mutations in the frataxin gene. Frataxin homologues, including bacterial CyaY proteins, can be found in most species and play a fundamental role in mitochondrial iron homeostasis, either promoting iron assembly into metaloproteins or contributing to iron detoxification. While several lines of evidence suggest that eukaryotic frataxins are more effective than bacterial ones in iron detoxification, the residues involved in this gain of function are unknown. In this work, we analyze conservation of amino acid sequence and protein structure among frataxins and CyaY proteins to identify four highly conserved residue clusters and group them into potential functional clusters. Clusters 1, 2, and 4 are present in eukaryotic frataxins and bacterial CyaY proteins. Cluster 3, containing two serines, a tyrosine, and a glutamate, is only present in eukaryotic frataxins and on CyaY proteins from the Rickettsia genus. Residues from cluster 3 are blocking a small cavity of about 40 Å present in E. coli's CyaY. The function of this cluster is unknown, but we hypothesize that its tyrosine may contribute to prevent formation of reactive oxygen species during iron detoxification. This cluster provides an example of gain of function during evolution in a protein involved in iron homeostasis, as our results suggests that Cluster 3 was present in the endosymbiont ancestor of mitochondria and was conserved in eukaryotic frataxins.}, } @article {pmid36360198, year = {2022}, author = {Boulygina, E and Sharko, F and Cheprasov, M and Gladysheva-Azgari, M and Slobodova, N and Tsygankova, S and Rastorguev, S and Grigorieva, L and Kopp, M and Fernandes, JMO and Novgorodov, G and Boeskorov, G and Protopopov, A and Hwang, WS and Tikhonov, A and Nedoluzhko, A}, title = {Ancient DNA Reveals Maternal Philopatry of the Northeast Eurasian Brown Bear (Ursus arctos) Population during the Holocene.}, journal = {Genes}, volume = {13}, number = {11}, pages = {}, pmid = {36360198}, issn = {2073-4425}, mesh = {Animals ; *Ursidae/genetics ; DNA, Ancient ; Phylogeny ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {Significant palaeoecological and paleoclimatic changes that took place during Late Pleistocene-Early Holocene transition are considered important factors that led to megafauna extinctions. Unlike many other species, the brown bear (Ursus arctos) has survived this geological time. Despite the fact that several mitochondrial DNA clades of brown bears became extinct at the end of the Pleistocene, this species is still widely distributed in Northeast Eurasia. Here, using the ancient DNA analysis of a brown bear individual that inhabited Northeast Asia in the Middle Holocene (3460 ± 40 years BP) and comparative phylogenetic analysis, we show a significant mitochondrial DNA similarity of the studied specimen with modern brown bears inhabiting Yakutia and Chukotka. In this study, we clearly demonstrate the maternal philopatry of the Northeastern Eurasian U. arctos population during the several thousand years of the Holocene.}, } @article {pmid36360182, year = {2022}, author = {Wang, Y and Hua, X and Shi, X and Wang, C}, title = {Origin, Evolution, and Research Development of Donkeys.}, journal = {Genes}, volume = {13}, number = {11}, pages = {}, pmid = {36360182}, issn = {2073-4425}, mesh = {Animals ; *Equidae/genetics ; *Microsatellite Repeats ; Genome/genetics ; Genomics ; Mitochondria/genetics ; }, abstract = {Lack of archaeological and whole-genome diversity data has restricted current knowledge of the evolutionary history of donkeys. With the advancement of science and technology, the discovery of archaeological evidence, the development of molecular genetics, and the improvement of whole-genome sequencing technology, the in-depth understanding of the origin and domestication of donkeys has been enhanced, however. Given the lack of systematic research, the present study carefully screened and collected multiple academic papers and books, journals, and literature on donkeys over the past 15 years. The origin and domestication of donkeys are reviewed in this paper from the aspects of basic information, cultural origin, bioarcheology, mitochondrial and chromosomal microsatellite sequences, and whole-genome sequence comparison. It also highlights and reviews genome assembly technology, by assembling the genome of an individual organism and comparing it with related sample genomes, which can be used to produce more accurate results through big data statistics, analysis, and computational correlation models. Background: The donkey industry in the world and especially in China is developing rapidly, and donkey farming is transforming gradually from the family farming model to large-scale, intensive, and integrated industrial operations, which could ensure the stability of product quality and quantity. However, theoretical research on donkey breeding and its technical development lags far behind that of other livestock, thereby limiting its industrial development. This review provides holistic information for the donkey industry and researchers, that could promote theoretical research, genomic selection (GS), and reproductive management of the donkey population.}, } @article {pmid36355348, year = {2023}, author = {Klucnika, A and Mu, P and Jezek, J and McCormack, M and Di, Y and Bradshaw, CR and Ma, H}, title = {REC drives recombination to repair double-strand breaks in animal mtDNA.}, journal = {The Journal of cell biology}, volume = {222}, number = {1}, pages = {}, pmid = {36355348}, issn = {1540-8140}, support = {803852/ERC_/European Research Council/International ; C6946/A24843/CRUK_/Cancer Research UK/United Kingdom ; 203144/WT_/Wellcome Trust/United Kingdom ; 203767/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Humans ; *DNA Repair/genetics ; *DNA, Mitochondrial/genetics ; Drosophila/genetics ; *Drosophila Proteins/genetics ; Homologous Recombination ; Meiosis ; Mitochondria/genetics ; }, abstract = {Mechanisms that safeguard mitochondrial DNA (mtDNA) limit the accumulation of mutations linked to mitochondrial and age-related diseases. Yet, pathways that repair double-strand breaks (DSBs) in animal mitochondria are poorly understood. By performing a candidate screen for mtDNA repair proteins, we identify that REC-an MCM helicase that drives meiotic recombination in the nucleus-also localizes to mitochondria in Drosophila. We show that REC repairs mtDNA DSBs by homologous recombination in somatic and germline tissues. Moreover, REC prevents age-associated mtDNA mutations. We further show that MCM8, the human ortholog of REC, also localizes to mitochondria and limits the accumulation of mtDNA mutations. This study provides mechanistic insight into animal mtDNA recombination and demonstrates its importance in safeguarding mtDNA during ageing and evolution.}, } @article {pmid36355038, year = {2022}, author = {Raval, PK and Garg, SG and Gould, SB}, title = {Endosymbiotic selective pressure at the origin of eukaryotic cell biology.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36355038}, issn = {2050-084X}, mesh = {*Eukaryotic Cells/physiology ; *Symbiosis/genetics ; Biological Evolution ; Eukaryota/genetics ; Archaea/genetics ; Cell Nucleus ; Meiosis ; Biology ; Phylogeny ; }, abstract = {The dichotomy that separates prokaryotic from eukaryotic cells runs deep. The transition from pro- to eukaryote evolution is poorly understood due to a lack of reliable intermediate forms and definitions regarding the nature of the first host that could no longer be considered a prokaryote, the first eukaryotic common ancestor, FECA. The last eukaryotic common ancestor, LECA, was a complex cell that united all traits characterising eukaryotic biology including a mitochondrion. The role of the endosymbiotic organelle in this radical transition towards complex life forms is, however, sometimes questioned. In particular the discovery of the asgard archaea has stimulated discussions regarding the pre-endosymbiotic complexity of FECA. Here we review differences and similarities among models that view eukaryotic traits as isolated coincidental events in asgard archaeal evolution or, on the contrary, as a result of and in response to endosymbiosis. Inspecting eukaryotic traits from the perspective of the endosymbiont uncovers that eukaryotic cell biology can be explained as having evolved as a solution to housing a semi-autonomous organelle and why the addition of another endosymbiont, the plastid, added no extra compartments. Mitochondria provided the selective pressures for the origin (and continued maintenance) of eukaryotic cell complexity. Moreover, they also provided the energetic benefit throughout eukaryogenesis for evolving thousands of gene families unique to eukaryotes. Hence, a synthesis of the current data lets us conclude that traits such as the Golgi apparatus, the nucleus, autophagosomes, and meiosis and sex evolved as a response to the selective pressures an endosymbiont imposes.}, } @article {pmid36353057, year = {2022}, author = {Liang, P and Wang, S and Lin, Y and Wang, L and Zhao, L and Liu, S}, title = {The complete mitochondrial genome of Cepola schlegelii from the East China Sea.}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {7}, number = {11}, pages = {1925-1927}, pmid = {36353057}, issn = {2380-2359}, abstract = {Cepola schlegelii (Bleeker 1854) belongs to the genus Cepola in the family Cepolidae and order Priacanthiformes. The complete mitochondrial genome of C. schlegelii was sequenced and analyzed by a high-throughput sequencing approach. The full length of the genome is 17,020 bp, including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and a non-coding control region (D-loop). Phylogenetic analysis based on complete mitochondrial genomes revealed that C. schlegelii was most closely related to Acanthocepola krusensternii. The complete mitochondrial sequence of C. schlegelii will enrich the mitochondrial genome database and provide useful resources for population genetics and evolution analyses.}, } @article {pmid36330786, year = {2022}, author = {De, AK and Bhattacharya, D and Sawhney, S and Bala, P and Sunder, J and Sujatha, T and Ponraj, P and Chakurkar, EB}, title = {Molecular characterization of Rhipicephalus microplus in Andaman and Nicobar Islands, India: an insight into genetic assemblages.}, journal = {Journal of genetics}, volume = {101}, number = {}, pages = {}, pmid = {36330786}, issn = {0973-7731}, mesh = {Animals ; *Rhipicephalus/genetics ; Phylogeny ; Haplotypes ; Geography ; Mitochondria/genetics ; India ; Islands ; }, abstract = {The tick, Rhipicephalus microplus is considered as the most notorious ectoparasite of veterinary importance in tropical and sub-tropical regions of the world. The present study deals with the molecular characterization of R. microplus in different regions of Andaman and Nicobar Islands using sequence information of mitochondrial cytochrome C oxidase subunit I (COX1) and their phylogenetic relationship with other Indian R. microplus genotypes. DNA polymorphism study identified a total of eight haplotypes with haplotype diversity of 0.909 ± 0.065 and nucleotide diversity of 0.01911 ± 0.00493. Currently, R. microplus complex consists of five taxa; R. microplus clade A sensu Burger et al. (2014), R. microplus clade B sensu Burger et al. (2014), R. microplus clade C sensu Low et al. (2015), R. australis and R. annulatus. Phylogenetic analysis revealed the presence of two clades (clade A and clade C) of R. microplus in Andaman and Nicobar isolates; Nicobar isolates belonged to clade A whereas Andaman isolates belonged to clade C of R. microplus complex. All the other Indian sequences retrieved from GenBank belonged to clade C of R. microplus complex. Andaman isolates under clade C of R. microplus were phylogenetically distinct from Indian isolates, which indicates independent speciation under isolated island milieu. In Indian isolates, no host-specific or geographical location-specific sub-clustering was observed which indicates the species jumping potential of the R. microplus tick. Therefore, this study indicated the presence of two different genetic makeup of R. microplus complex in two areas of the Andaman and Nicobar archipelago separated by a natural geographical barrier. This indicates presence of two different founding populations of ticks, one in the south and north-middle Andaman and the other in Nicobar Island.}, } @article {pmid36324074, year = {2022}, author = {Zhao, B and Gao, S and Zhao, M and Lv, H and Song, J and Wang, H and Zeng, Q and Liu, J}, title = {Mitochondrial genomic analyses provide new insights into the "missing" atp8 and adaptive evolution of Mytilidae.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {738}, pmid = {36324074}, issn = {1471-2164}, mesh = {Animals ; *Genome, Mitochondrial ; *Mytilidae/genetics ; Phylogeny ; Genes, Mitochondrial ; Mitochondrial Proton-Translocating ATPases/genetics ; Genomics/methods ; }, abstract = {BACKGROUND: Mytilidae, also known as marine mussels, are widely distributed in the oceans worldwide. Members of Mytilidae show a tremendous range of ecological adaptions, from the species distributed in freshwater to those that inhabit in deep-sea. Mitochondria play an important role in energy metabolism, which might contribute to the adaptation of Mytilidae to different environments. In addition, some bivalve species are thought to lack the mitochondrial protein-coding gene ATP synthase F0 subunit 8. Increasing studies indicated that the absence of atp8 may be caused by annotation difficulties for atp8 gene is characterized by highly divergent, variable length.

RESULTS: In this study, the complete mitochondrial genomes of three marine mussels (Xenostrobus securis, Bathymodiolus puteoserpentis, Gigantidas vrijenhoeki) were newly assembled, with the lengths of 14,972 bp, 20,482, and 17,786 bp, respectively. We annotated atp8 in the sequences that we assembled and the sequences lacking atp8. The newly annotated atp8 sequences all have one predicted transmembrane domain, a similar hydropathy profile, as well as the C-terminal region with positively charged amino acids. Furthermore, we reconstructed the phylogenetic trees and performed positive selection analysis. The results showed that the deep-sea bathymodiolines experienced more relaxed evolutionary constraints. And signatures of positive selection were detected in nad4 of Limnoperna fortunei, which may contribute to the survival and/or thriving of this species in freshwater.

CONCLUSIONS: Our analysis supported that atp8 may not be missing in the Mytilidae. And our results provided evidence that the mitochondrial genes may contribute to the adaptation of Mytilidae to different environments.}, } @article {pmid36323233, year = {2022}, author = {Picard, M and Shirihai, OS}, title = {Mitochondrial signal transduction.}, journal = {Cell metabolism}, volume = {34}, number = {11}, pages = {1620-1653}, pmid = {36323233}, issn = {1932-7420}, support = {R01 AG066828/AG/NIA NIH HHS/United States ; R21 MH123927/MH/NIMH NIH HHS/United States ; R35 GM119793/GM/NIGMS NIH HHS/United States ; R01 MH119336/MH/NIMH NIH HHS/United States ; R01 MH122706/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Mitochondria/metabolism ; *Signal Transduction ; Cell Communication ; Cell Nucleus/metabolism ; }, abstract = {The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. We argue that mitochondria are the processor of the cell, and together with the nucleus and other organelles they constitute the mitochondrial information processing system (MIPS). In a three-step process, mitochondria (1) sense and respond to both endogenous and environmental inputs through morphological and functional remodeling; (2) integrate information through dynamic, network-based physical interactions and diffusion mechanisms; and (3) produce output signals that tune the functions of other organelles and systemically regulate physiology. This input-to-output transformation allows mitochondria to transduce metabolic, biochemical, neuroendocrine, and other local or systemic signals that enhance organismal adaptation. An explicit focus on mitochondrial signal transduction emphasizes the role of communication in mitochondrial biology. This framework also opens new avenues to understand how mitochondria mediate inter-organ processes underlying human health.}, } @article {pmid36321837, year = {2022}, author = {McGlynn, SE and Perkins, G and Sim, MS and Mackey, M and Deerinck, TJ and Thor, A and Phan, S and Ballard, D and Ellisman, MH and Orphan, VJ}, title = {A Cristae-Like Microcompartment in Desulfobacterota.}, journal = {mBio}, volume = {13}, number = {6}, pages = {e0161322}, pmid = {36321837}, issn = {2150-7511}, abstract = {Some Alphaproteobacteria contain intracytoplasmic membranes (ICMs) and proteins homologous to those responsible for the mitochondrial cristae, an observation which has given rise to the hypothesis that the Alphaproteobacteria endosymbiont had already evolved cristae-like structures and functions. However, our knowledge of microbial fine structure is still limited, leaving open the possibility of structurally homologous ICMs outside the Alphaproteobacteria. Here, we report on the detailed characterization of lamellar cristae-like ICMs in environmental sulfate-reducing Desulfobacterota that form syntrophic partnerships with anaerobic methane-oxidizing (ANME) archaea. These structures are junction-bound to the cytoplasmic membrane and resemble the form seen in the lamellar cristae of opisthokont mitochondria. Extending these observations, we also characterized similar structures in Desulfovibrio carbinolicus, a close relative of the magnetotactic D. magneticus, which does not contain magnetosomes. Despite a remarkable structural similarity, the key proteins involved in cristae formation have not yet been identified in Desulfobacterota, suggesting that an analogous, but not a homologous, protein organization system developed during the evolution of some members of Desulfobacterota. IMPORTANCE Working with anaerobic consortia of methane oxidizing ANME archaea and their sulfate-reducing bacterial partners recovered from deep sea sediments and with the related sulfate-reducing bacterial isolate D. carbinolicus, we discovered that their intracytoplasmic membranes (ICMs) appear remarkably similar to lamellar cristae. Three-dimensional electron microscopy allowed for the novel analysis of the nanoscale attachment of ICMs to the cytoplasmic membrane, and these ICMs are structurally nearly identical to the crista junction architecture seen in metazoan mitochondria. However, the core junction-forming proteins must be different. The outer membrane vesicles were observed to bud from syntrophic Desulfobacterota, and darkly stained granules were prominent in both Desulfobacterota and D. carbinolicus. These findings expand the taxonomic breadth of ICM-producing microorganisms and add to our understanding of three-dimensional microbial fine structure in environmental microorganisms.}, } @article {pmid36309009, year = {2022}, author = {Liu, Y and Zhou, J and Zhang, N and Wu, X and Zhang, Q and Zhang, W and Li, X and Tian, Y}, title = {Two sensory neurons coordinate the systemic mitochondrial stress response via GPCR signaling in C. elegans.}, journal = {Developmental cell}, volume = {57}, number = {21}, pages = {2469-2482.e5}, doi = {10.1016/j.devcel.2022.10.001}, pmid = {36309009}, issn = {1878-1551}, mesh = {Animals ; *Caenorhabditis elegans/metabolism ; *Caenorhabditis elegans Proteins/genetics/metabolism ; Mitochondria/metabolism ; Unfolded Protein Response ; Sensory Receptor Cells/metabolism ; Receptors, G-Protein-Coupled/genetics/metabolism ; }, abstract = {Mitochondrial perturbations within neurons communicate stress signals to peripheral tissues, coordinating organismal-wide mitochondrial homeostasis for optimal fitness. However, the neuronal control of the systemic stress regulation remains poorly understood. Here, we identified a G-protein-coupled receptor (GPCR), SRZ-75, that couples with Gαq signaling in a pair of chemosensory ADL neurons to drive the mitochondrial unfolded protein response (UPR[mt]) activation in the intestine via the release of neuropeptides in Caenorhabditis elegans. Constitutive activation of Gαq signaling in the ADL neurons is sufficient to induce the intestinal UPR[mt], leading to increased stress resistance and metabolic adaptations. Ablation of ADL neurons attenuates the intestinal UPR[mt] activation in response to various forms of neuronal mitochondrial dysfunction. Thus, GPCR and its Gαq downstream signaling in two sensory neurons coordinate the systemic UPR[mt] activation, representing a previously uncharacterized, but potentially conserved, neuronal signaling for organismal-wide mitochondrial stress regulation.}, } @article {pmid36293209, year = {2022}, author = {Liu, Q and Zhang, L and Zou, Y and Tao, Y and Wang, B and Li, B and Liu, R and Wang, B and Ding, L and Cui, Q and Lin, J and Mao, B and Xiong, W and Yu, M}, title = {Modulating p-AMPK/mTOR Pathway of Mitochondrial Dysfunction Caused by MTERF1 Abnormal Expression in Colorectal Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {20}, pages = {}, pmid = {36293209}, issn = {1422-0067}, mesh = {Humans ; AMP-Activated Protein Kinases/metabolism ; Reactive Oxygen Species/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Cell Proliferation/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/metabolism ; HCT116 Cells ; Cell Line, Tumor ; *Colonic Neoplasms/metabolism ; Adenosine Triphosphate/metabolism ; *Colorectal Neoplasms/pathology ; Gene Expression Regulation, Neoplastic ; }, abstract = {Human mitochondrial transcription termination factor 1 (MTERF1) has been demonstrated to play an important role in mitochondrial gene expression regulation. However, the molecular mechanism of MTERF1 in colorectal cancer (CRC) remains largely unknown. Here, we found that MTERF1 expression was significantly increased in colon cancer tissues compared with normal colorectal tissue by Western blotting, immunohistochemistry, and tissue microarrays (TMA). Overexpression of MTERF1 in the HT29 cell promoted cell proliferation, migration, invasion, and xenograft tumor formation, whereas knockdown of MTERF1 in HCT116 cells appeared to be the opposite phenotype to HT29 cells. Furthermore, MTERF1 can increase mitochondrial DNA (mtDNA) replication, transcription, and protein synthesis in colorectal cancer cells; increase ATP levels, the mitochondrial crista density, mitochondrial membrane potential, and oxygen consumption rate (OCR); and reduce the ROS production in colorectal cancer cells, thereby enhancing mitochondrial oxidative phosphorylation (OXPHOS) activity. Mechanistically, we revealed that MTERF1 regulates the AMPK/mTOR signaling pathway in cancerous cell lines, and we also confirmed the involvement of the AMPK/mTOR signaling pathway in both xenograft tumor tissues and colorectal cancer tissues. In summary, our data reveal an oncogenic role of MTERF1 in CRC progression, indicating that MTERF1 may represent a new therapeutic target in the future.}, } @article {pmid36288802, year = {2022}, author = {Weaver, RJ and Rabinowitz, S and Thueson, K and Havird, JC}, title = {Genomic Signatures of Mitonuclear Coevolution in Mammals.}, journal = {Molecular biology and evolution}, volume = {39}, number = {11}, pages = {}, pmid = {36288802}, issn = {1537-1719}, support = {R35 GM142836/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Genes, Mitochondrial ; Mammals/genetics ; Cell Nucleus/genetics ; Mitochondrial Proteins/genetics ; Genomics ; }, abstract = {Mitochondrial (mt) and nuclear-encoded proteins are integrated in aerobic respiration, requiring co-functionality among gene products from fundamentally different genomes. Different evolutionary rates, inheritance mechanisms, and selection pressures set the stage for incompatibilities between interacting products of the two genomes. The mitonuclear coevolution hypothesis posits that incompatibilities may be avoided if evolution in one genome selects for complementary changes in interacting genes encoded by the other genome. Nuclear compensation, in which deleterious mtDNA changes are offset by compensatory nuclear changes, is often invoked as the primary mechanism for mitonuclear coevolution. Yet, direct evidence supporting nuclear compensation is rare. Here, we used data from 58 mammalian species representing eight orders to show strong correlations between evolutionary rates of mt and nuclear-encoded mt-targeted (N-mt) proteins, but not between mt and non-mt-targeted nuclear proteins, providing strong support for mitonuclear coevolution across mammals. N-mt genes with direct mt interactions also showed the strongest correlations. Although most N-mt genes had elevated dN/dS ratios compared to mt genes (as predicted under nuclear compensation), N-mt sites in close contact with mt proteins were not overrepresented for signs of positive selection compared to noncontact N-mt sites (contrary to predictions of nuclear compensation). Furthermore, temporal patterns of N-mt and mt amino acid substitutions did not support predictions of nuclear compensation, even in positively selected, functionally important residues with direct mitonuclear contacts. Overall, our results strongly support mitonuclear coevolution across ∼170 million years of mammalian evolution but fail to support nuclear compensation as the major mode of mitonuclear coevolution.}, } @article {pmid36281555, year = {2022}, author = {Guo, C and Wang, A and Cheng, H and Chen, L}, title = {New imaging instrument in animal models: Two-photon miniature microscope and large field of view miniature microscope for freely behaving animals.}, journal = {Journal of neurochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1111/jnc.15711}, pmid = {36281555}, issn = {1471-4159}, abstract = {Over the past decade, novel optical imaging tools have been developed for imaging neuronal activities along with the evolution of fluorescence indicators with brighter expression and higher sensitivity. Miniature microscopes, as revolutionary approaches, enable the imaging of large populations of neuron ensembles in freely behaving rodents and mammals, which allows exploring the neural basis of behaviors. Recent progress in two-photon miniature microscopes and mesoscale single-photon miniature microscopes further expand those affordable methods to navigate neural activities during naturalistic behaviors. In this review article, two-photon miniature microscopy techniques are summarized historically from the first documented attempt to the latest ones, and comparisons are made. The driving force behind and their potential for neuroscientific inquiries are also discussed. Current progress in terms of the mesoscale, i.e., the large field-of-view miniature microscopy technique, is addressed as well. Then, pipelines for registering single cells from the data of two-photon and large field-of-view miniature microscopes are discussed. Finally, we present the potential evolution of the techniques.}, } @article {pmid36280780, year = {2022}, author = {Martijn, J and Vosseberg, J and Guy, L and Offre, P and Ettema, TJG}, title = {Phylogenetic affiliation of mitochondria with Alpha-II and Rickettsiales is an artefact.}, journal = {Nature ecology & evolution}, volume = {6}, number = {12}, pages = {1829-1831}, pmid = {36280780}, issn = {2397-334X}, mesh = {*Rickettsiales ; Phylogeny ; *Artifacts ; Mitochondria ; }, } @article {pmid36280779, year = {2022}, author = {Fan, L and Wu, D and Goremykin, V and Trost, K and Knopp, M and Zhang, C and Martin, WF and Zhu, R}, title = {Reply to: Phylogenetic affiliation of mitochondria with Alpha-II and Rickettsiales is an artefact.}, journal = {Nature ecology & evolution}, volume = {6}, number = {12}, pages = {1832-1835}, pmid = {36280779}, issn = {2397-334X}, mesh = {*Rickettsiales ; Phylogeny ; *Artifacts ; Mitochondria ; }, } @article {pmid36275864, year = {2022}, author = {Bi, R and Li, Y and Xu, M and Zheng, Q and Zhang, DF and Li, X and Ma, G and Xiang, B and Zhu, X and Zhao, H and Huang, X and Zheng, P and Yao, YG}, title = {Direct evidence of CRISPR-Cas9-mediated mitochondrial genome editing.}, journal = {Innovation (Cambridge (Mass.))}, volume = {3}, number = {6}, pages = {100329}, pmid = {36275864}, issn = {2666-6758}, abstract = {Pathogenic mitochondrial DNA (mtDNA) mutations can cause a variety of human diseases. The recent development of genome-editing technologies to manipulate mtDNA, such as mitochondria-targeted DNA nucleases and base editors, offer a promising way for curing mitochondrial diseases caused by mtDNA mutations. The CRISPR-Cas9 system is a widely used tool for genome editing; however, its application in mtDNA editing is still under debate. In this study, we developed a mito-Cas9 system by adding the mitochondria-targeted sequences and 3' untranslated region of nuclear-encoded mitochondrial genes upstream and downstream of the Cas9 gene, respectively. We confirmed that the mito-Cas9 system was transported into mitochondria and enabled knockin of exogenous single-stranded DNA oligonucleotides (ssODNs) into mtDNA based on proteinase and DNase protection assays. Successful knockin of exogenous ssODNs into mtDNA was further validated using polymerase chain reaction-free third-generation sequencing technology. We also demonstrated that RS-1, an agonist of RAD51, significantly increased knockin efficiency of the mito-Cas9 system. Collectively, we provide direct evidence that mtDNA can be edited using the CRISPR-Cas9 system. The mito-Cas9 system could be optimized as a promising approach for the treatment of mitochondrial diseases caused by pathogenic mtDNA mutations, especially those with homoplasmic mtDNA mutations.}, } @article {pmid36271979, year = {2022}, author = {Hajibarat, Z and Saidi, A and Gorji, AM and Zeinalabedini, M and Ghaffari, MR and Hajibarat, Z and Nasrollahi, A}, title = {Identification of myosin genes and their expression in response to biotic (PVY, PVX, PVS, and PVA) and abiotic (Drought, Heat, Cold, and High-light) stress conditions in potato.}, journal = {Molecular biology reports}, volume = {49}, number = {12}, pages = {11983-11996}, pmid = {36271979}, issn = {1573-4978}, mesh = {*Solanum tuberosum/genetics/metabolism ; Droughts ; Phylogeny ; Plant Proteins/metabolism ; Hot Temperature ; Plant Breeding ; Stress, Physiological/genetics ; Plants/metabolism ; Myosins/genetics/metabolism ; Gene Expression Regulation, Plant/genetics ; }, abstract = {BACKGROUND: Plant organelles are highly motile where their movement is significant for fast distribution of material around the cell, facilitation of the plant's ability to respond to abiotic and biotic signals, and for appropriate growth. Abiotic and biotic stresses are among the major factors limiting crop yields, and biological membranes are the first target of these stresses. Plants utilize adaptive mechanisms namely myosin to repair injured membranes following exposure to abiotic and biotic stresses.

OBJECTIVE: Due to the economic importance and cultivation of potato grown under abiotic and biotic stress prone areas, identification and characterization of myosin family members in potato were performed in the present research.

METHODS: To identify the myosin genes in potato, we performed genome-wide analysis of myosin genes in the S. tuberosum genome using the phytozome. All putative sequences were approved with the interproscan. Bioinformatics analysis was conducted using phylogenetic tree, gene structure, cis-regulatory elements, protein-protein interaction, and gene expression.

RESULT: The majority of the cell machinery contain actin cytoskeleton and myosins, where motility of organelles are dependent on them. Homology-based analysis was applied to determine seven myosin genes in the potato genome. The members of myosin could be categorized into two groups (XI and VIII). Some of myosin proteins were sub-cellularly located in the nucleus containing 71.5% of myosin proteins and other myosin proteins were localized in the mitochondria, plasma-membrane, and cytoplasm. Determination of co-expressed network, promoter analysis, and gene structure were also performed and gene expression pattern of each gene was surveyed. Number of introns in the gene family members varied from 1 to 39. Gene expression analysis demonstrated that StMyoXI-B and StMyoVIII-2 had the highest transcripts, induced by biotic and abiotic stresses in all three tissues of stem, root, and leaves, respectively. Overall, different cis-elements including abiotic and biotic responsive, hormonal responsive, light responsive, defense responsive elements were found in the myosin promoter sequences. Among the cis-elements, the MYB, G-box, ABRE, JA, and SA contributed the most in the plant growth and development, and in response to abiotic and biotic stress conditions.

CONCLUSION: Our results showed that myosin genes can be utilized in breeding programs and genetic engineering of plants with the aim of increasing tolerance to abiotic and biotic stresses, especially to viral stresses such as PVY, PVX, PVA, PVS, high light, drought, cold and heat.}, } @article {pmid36260528, year = {2022}, author = {Zhang, K and Li, J and Li, G and Zhao, Y and Dong, Y and Zhang, Y and Sun, W and Wang, J and Yao, J and Ma, Y and Wang, H and Zhang, Z and Wang, T and Xie, K and Wendel, JF and Liu, B and Gong, L}, title = {Compensatory Genetic and Transcriptional Cytonuclear Coordination in Allopolyploid Lager Yeast (Saccharomyces pastorianus).}, journal = {Molecular biology and evolution}, volume = {39}, number = {11}, pages = {}, pmid = {36260528}, issn = {1537-1719}, mesh = {*Beer ; *Gene Conversion ; Genome ; Cell Nucleus/genetics ; }, abstract = {Cytonuclear coordination between biparental-nuclear genomes and uniparental-cytoplasmic organellar genomes in plants is often resolved by genetic and transcriptional cytonuclear responses. Whether this mechanism also acts in allopolyploid members of other kingdoms is not clear. Additionally, cytonuclear coordination of interleaved allopolyploid cells/individuals within the same population is underexplored. The yeast Saccharomyces pastorianus provides the opportunity to explore cytonuclear coevolution during different growth stages and from novel dimensions. Using S. pastorianus cells from multiple growth stages in the same environment, we show that nuclear mitochondria-targeted genes have undergone both asymmetric gene conversion and growth stage-specific biased expression favoring genes from the mitochondrial genome donor (Saccharomyces eubayanus). Our results suggest that cytonuclear coordination in allopolyploid lager yeast species entails an orchestrated and compensatory genetic and transcriptional evolutionary regulatory shift. The common as well as unique properties of cytonuclear coordination underlying allopolyploidy between unicellular yeasts and higher plants offers novel insights into mechanisms of cytonuclear evolution associated with allopolyploid speciation.}, } @article {pmid36255631, year = {2023}, author = {Marx, C and Marx-Blümel, L and Sonnemann, J and Wang, ZQ}, title = {Assessment of Mitochondrial Dysfunctions After Sirtuin Inhibition.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2589}, number = {}, pages = {269-291}, pmid = {36255631}, issn = {1940-6029}, mesh = {*Sirtuins/metabolism ; Lysine/metabolism ; Phylogeny ; Acetylation ; Histone Deacetylases/metabolism ; Histone Acetyltransferases/metabolism ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; Histone Deacetylase Inhibitors/pharmacology ; }, abstract = {Posttranslational modifications are important for protein functions and cellular signaling pathways. The acetylation of lysine residues is catalyzed by histone acetyltransferases (HATs) and removed by histone deacetylases (HDACs), with the latter being grouped into four phylogenetic classes. The class III of the HDAC family, the sirtuins (SIRTs), contributes to gene expression, genomic stability, cell metabolism, and tumorigenesis. Thus, several specific SIRT inhibitors (SIRTi) have been developed to target cancer cell proliferation. Here we provide an overview of methods to study SIRT-dependent cell metabolism and mitochondrial functionality. The chapter describes metabolic flux analysis using Seahorse analyzers, methods for normalization of Seahorse data, flow cytometry and fluorescence microscopy to determine the mitochondrial membrane potential, mitochondrial content per cell and mitochondrial network structures, and Western blot analysis to measure mitochondrial proteins.}, } @article {pmid36253367, year = {2022}, author = {Tobiasson, V and Berzina, I and Amunts, A}, title = {Structure of a mitochondrial ribosome with fragmented rRNA in complex with membrane-targeting elements.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6132}, pmid = {36253367}, issn = {2041-1723}, mesh = {*Chlorophyta/metabolism ; Mitochondria/metabolism ; *Mitochondrial Ribosomes/metabolism ; RNA, Ribosomal/metabolism ; RNA, Ribosomal, 5S/metabolism ; Ribosomes/metabolism ; }, abstract = {Mitoribosomes of green algae display a great structural divergence from their tracheophyte relatives, with fragmentation of both rRNA and proteins as a defining feature. Here, we report a 2.9 Å resolution structure of the mitoribosome from the alga Polytomella magna harbouring a reduced rRNA split into 13 fragments. We found that the rRNA contains a non-canonical reduced form of the 5S, as well as a permutation of the LSU domain I. The mt-5S rRNA is stabilised by mL40 that is also found in mitoribosomes lacking the 5S, which suggests an evolutionary pathway. Through comparison to other ribosomes with fragmented rRNAs, we observe that the pattern is shared across large evolutionary distances, and between cellular compartments, indicating an evolutionary convergence and supporting the concept of a primordial fragmented ribosome. On the protein level, eleven peripherally associated HEAT-repeat proteins are involved in the binding of 3' rRNA termini, and the structure features a prominent pseudo-trimer of one of them (mL116). Finally, in the exit tunnel, mL128 constricts the tunnel width of the vestibular area, and mL105, a homolog of a membrane targeting component mediates contacts with an inner membrane bound insertase. Together, the structural analysis provides insight into the evolution of the ribosomal machinery in mitochondria.}, } @article {pmid36251232, year = {2023}, author = {Giuditta, A and Zucconi, GG and Sadile, A}, title = {Brain Metabolic DNA: A Long Story and Some Conclusions.}, journal = {Molecular neurobiology}, volume = {60}, number = {1}, pages = {228-234}, pmid = {36251232}, issn = {1559-1182}, mesh = {Animals ; Humans ; Mice ; *DNA/metabolism ; *Mitochondria/metabolism ; Brain/metabolism ; Cytoplasm/metabolism ; RNA/metabolism ; DNA, Mitochondrial/metabolism ; }, abstract = {We have previously outlined the main properties of brain metabolic DNA (BMD) and its involvement in circadian oscillations, learning, and post-trial sleep. The presence of BMD in certain subcellular fractions and their behavior in cesium gradients have suggested that BMD originates from cytoplasmic reverse transcription and subsequently acquires a double-stranded configuration. More recently, it has been reported that some DNA sequences of cytoplasmic BMD in learning mice are different from that of the control animals. Furthermore, BMD is located in vicinity of the genes involved in different modifications of synaptic activity, suggesting that BMD may contribute to the brain's response to the changing environment. The present review outlines recent data with a special emphasis on reverse transcription of BMD that may recapitulate the molecular events at the time of the "RNA world" by activating mitochondrial telomerase and generating RNA templates from mitochondrial transcripts. The latter unexpected role of mitochondria is likely to promote a better understanding of mitochondrial contribution to cellular interactions and eukaryotic evolution. An initial step regards the role of human mitochondria in embryonic BMD synthesis, which is exclusively of maternal origin. In addition, mitochondrial transcripts involved in reverse transcription of BMD might possibly reveal unexpected features elucidating mitochondrial involvement in cancer events and neurodegenerative disorders.}, } @article {pmid36227729, year = {2022}, author = {Loiacono, FV and Walther, D and Seeger, S and Thiele, W and Gerlach, I and Karcher, D and Schöttler, MA and Zoschke, R and Bock, R}, title = {Emergence of Novel RNA-Editing Sites by Changes in the Binding Affinity of a Conserved PPR Protein.}, journal = {Molecular biology and evolution}, volume = {39}, number = {12}, pages = {}, pmid = {36227729}, issn = {1537-1719}, mesh = {RNA Editing ; *Arabidopsis Proteins/genetics/metabolism ; *Arabidopsis/genetics/metabolism ; Chloroplasts/metabolism ; RNA ; Plant Proteins/genetics/metabolism ; }, abstract = {RNA editing converts cytidines to uridines in plant organellar transcripts. Editing typically restores codons for conserved amino acids. During evolution, specific C-to-U editing sites can be lost from some plant lineages by genomic C-to-T mutations. By contrast, the emergence of novel editing sites is less well documented. Editing sites are recognized by pentatricopeptide repeat (PPR) proteins with high specificity. RNA recognition by PPR proteins is partially predictable, but prediction is often inadequate for PPRs involved in RNA editing. Here we have characterized evolution and recognition of a recently gained editing site. We demonstrate that changes in the RNA recognition motifs that are not explainable with the current PPR code allow an ancient PPR protein, QED1, to uniquely target the ndhB-291 site in Brassicaceae. When expressed in tobacco, the Arabidopsis QED1 edits 33 high-confident off-target sites in chloroplasts and mitochondria causing a spectrum of mutant phenotypes. By manipulating the relative expression levels of QED1 and ndhB-291, we show that the target specificity of the PPR protein depends on the RNA:protein ratio. Finally, our data suggest that the low expression levels of PPR proteins are necessary to ensure the specificity of editing site selection and prevent deleterious off-target editing.}, } @article {pmid36226970, year = {2022}, author = {Chen, L and Kashina, A}, title = {Arginylation Regulates Cytoskeleton Organization and Cell Division and Affects Mitochondria in Fission Yeast.}, journal = {Molecular and cellular biology}, volume = {42}, number = {11}, pages = {e0026122}, pmid = {36226970}, issn = {1098-5549}, mesh = {Animals ; Mice ; *Schizosaccharomyces/genetics/metabolism ; Arginine/metabolism ; Cytoskeleton/metabolism ; Cell Division ; Mitochondria/metabolism ; *Biological Phenomena ; Mammals/metabolism ; }, abstract = {Protein arginylation mediated by arginyltransferase Ate1 is a posttranslational modification of emerging importance implicated in the regulation of mammalian embryogenesis, the cardiovascular system, tissue morphogenesis, cell migration, neurodegeneration, cancer, and aging. Ate1 deletion results in embryonic lethality in mice but does not affect yeast viability, making yeast an ideal system to study the molecular pathways regulated by arginylation. Here, we conducted a global analysis of cytoskeleton-related arginylation-dependent phenotypes in Schizosaccharomyces pombe, a fission yeast species that shares many fundamental features of higher eukaryotic cells. Our studies revealed roles of Ate1 in cell division, cell polarization, organelle transport, and interphase cytoskeleton organization and dynamics. We also found a role of Ate1 in mitochondria morphology and maintenance. Furthermore, targeted mass spectrometry analysis of the total Sc. pombe arginylome identified a number of arginylated proteins, including those that play direct roles in these processes; lack of their arginylation may be responsible for ate1-knockout phenotypes. Our work outlines global biological processes potentially regulated by arginylation and paves the way to unraveling the functions of protein arginylation that are conserved at multiple levels of evolution and potentially constitute the primary role of this modification in vivo.}, } @article {pmid36212359, year = {2022}, author = {Liu, S and Storti, M and Finazzi, G and Bowler, C and Dorrell, RG}, title = {A metabolic, phylogenomic and environmental atlas of diatom plastid transporters from the model species Phaeodactylum.}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {950467}, pmid = {36212359}, issn = {1664-462X}, abstract = {Diatoms are an important group of algae, contributing nearly 40% of total marine photosynthetic activity. However, the specific molecular agents and transporters underpinning the metabolic efficiency of the diatom plastid remain to be revealed. We performed in silico analyses of 70 predicted plastid transporters identified by genome-wide searches of Phaeodactylum tricornutum. We considered similarity with Arabidopsis thaliana plastid transporters, transcriptional co-regulation with genes encoding core plastid metabolic pathways and with genes encoded in the mitochondrial genomes, inferred evolutionary histories using single-gene phylogeny, and environmental expression trends using Tara Oceans meta-transcriptomics and meta-genomes data. Our data reveal diatoms conserve some of the ion, nucleotide and sugar plastid transporters associated with plants, such as non-specific triose phosphate transporters implicated in the transport of phosphorylated sugars, NTP/NDP and cation exchange transporters. However, our data also highlight the presence of diatom-specific transporter functions, such as carbon and amino acid transporters implicated in intricate plastid-mitochondria crosstalk events. These confirm previous observations that substrate non-specific triose phosphate transporters (TPT) may exist as principal transporters of phosphorylated sugars into and out of the diatom plastid, alongside suggesting probable agents of NTP exchange. Carbon and amino acid transport may be related to intricate metabolic plastid-mitochondria crosstalk. We additionally provide evidence from environmental meta-transcriptomic/meta- genomic data that plastid transporters may underpin diatom sensitivity to ocean warming, and identify a diatom plastid transporter (J43171) whose expression may be positively correlated with temperature.}, } @article {pmid36205366, year = {2022}, author = {Nofrianto, AB and Lawelle, SA and Mokodongan, DF and Masengi, KWA and Inomata, N and Hashiguchi, Y and Kitano, J and Sumarto, BKA and Kakioka, R and Yamahira, K}, title = {Ancient Admixture in Freshwater Halfbeaks of the Genus Nomorhamphus in Southeast Sulawesi.}, journal = {Zoological science}, volume = {39}, number = {5}, pages = {453-458}, doi = {10.2108/zs220023}, pmid = {36205366}, issn = {0289-0003}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Fresh Water ; Indonesia ; *Mitochondria/genetics ; Phylogeny ; Water ; }, abstract = {Freshwater halfbeaks of the genus Nomorhamphus (Zenarchopteridae) uniquely diversified on Sulawesi Island, where tectonic movements have been very active since the Pliocene. Most species of this genus have quite limited distributions, which indicates that geographic isolations have contributed to their diversification. In this study, we demonstrated that secondary contacts and resultant admixtures between long-isolated species/populations may have also been important. We found that the mitochondrial phylogeny of a group of Nomorhamphus in Southeast Sulawesi was discordant with the nuclear phylogeny. Most notably, individuals in the upper and lower streams of the Moramo River, a small river in this region, clustered with each other in the mitochondrial phylogeny but not in the nuclear phylogeny; in the latter, the lower-stream individuals formed a clade with individuals in the Anduna River, a different river with no present water connection to the Moramo River. Phylogenetic network and population structure analyses using genomic data obtained from RNA-seq revealed that the lower-stream Moramo population admixed with the upper-stream Moramo lineage in ancient times. These findings indicate that the observed mito-nuclear discordance was caused by mitochondrial introgression and not incomplete lineage sorting. The phylogenetic network also revealed several other admixtures between ancient lineages. Repeated admixtures were also evidenced by topological incongruence in population trees estimated using the RNA-seq data. We propose that activities of many fault systems dissecting Southeast Sulawesi caused repeated secondary contact.}, } @article {pmid36203893, year = {2022}, author = {Mondal, S and Singh, SP}, title = {New insights on thioredoxins (Trxs) and glutaredoxins (Grxs) by in silico amino acid sequence, phylogenetic and comparative structural analyses in organisms of three domains of life.}, journal = {Heliyon}, volume = {8}, number = {10}, pages = {e10776}, pmid = {36203893}, issn = {2405-8440}, abstract = {Thioredoxins (Trxs) and Glutaredoxins (Grxs) regulate several cellular processes by controlling the redox state of their target proteins. Trxs and Grxs belong to thioredoxin superfamily and possess characteristic Trx/Grx fold. Several phylogenetic, biochemical and structural studies have contributed to our overall understanding of Trxs and Grxs. However, comparative study of closely related Trxs and Grxs in organisms of all domains of life was missing. Here, we conducted in silico comparative structural analysis combined with amino acid sequence and phylogenetic analyses of 65 Trxs and 88 Grxs from 12 organisms of three domains of life to get insights into evolutionary and structural relationship of two proteins. Outcomes suggested that despite diversity in their amino acids composition in distantly related organisms, both Trxs and Grxs strictly conserved functionally and structurally important residues. Also, position of these residues was highly conserved in all studied Trxs and Grxs. Notably, if any substitution occurred during evolution, preference was given to amino acids having similar chemical properties. Trxs and Grxs were found more different in eukaryotes than prokaryotes due to altered helical conformation. The surface of Trxs was negatively charged, while Grxs surface was positively charged, however, the active site was constituted by uncharged amino acids in both proteins. Also, phylogenetic analysis of Trxs and Grxs in three domains of life supported endosymbiotic origins of chloroplast and mitochondria, and suggested their usefulness in molecular systematics. We also report previously unknown catalytic motifs of two proteins, and discuss in detail about effect of abovementioned parameters on overall structural and functional diversity of Trxs and Grxs.}, } @article {pmid36198798, year = {2022}, author = {Wei, W and Schon, KR and Elgar, G and Orioli, A and Tanguy, M and Giess, A and Tischkowitz, M and Caulfield, MJ and Chinnery, PF}, title = {Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes.}, journal = {Nature}, volume = {611}, number = {7934}, pages = {105-114}, pmid = {36198798}, issn = {1476-4687}, support = {212219/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; MC_UU_00015/9/MRC_/Medical Research Council/United Kingdom ; RPG-2018-408/WT_/Wellcome Trust/United Kingdom ; MR/S005021/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Cell Nucleus/genetics/metabolism ; *DNA, Mitochondrial/genetics/metabolism ; *Genome, Human/genetics ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA ; Mutation ; Liposarcoma, Myxoid/genetics ; Neoplasms/genetics ; Germ-Line Mutation ; DNA Breaks, Double-Stranded ; DNA Repair ; }, abstract = {DNA transfer from cytoplasmic organelles to the cell nucleus is a legacy of the endosymbiotic event-the majority of nuclear-mitochondrial segments (NUMTs) are thought to be ancient, preceding human speciation[1-3]. Here we analyse whole-genome sequences from 66,083 people-including 12,509 people with cancer-and demonstrate the ongoing transfer of mitochondrial DNA into the nucleus, contributing to a complex NUMT landscape. More than 99% of individuals had at least one of 1,637 different NUMTs, with 1 in 8 individuals having an ultra-rare NUMT that is present in less than 0.1% of the population. More than 90% of the extant NUMTs that we evaluated inserted into the nuclear genome after humans diverged from apes. Once embedded, the sequences were no longer under the evolutionary constraint seen within the mitochondrion, and NUMT-specific mutations had a different mutational signature to mitochondrial DNA. De novo NUMTs were observed in the germline once in every 10[4] births and once in every 10[3] cancers. NUMTs preferentially involved non-coding mitochondrial DNA, linking transcription and replication to their origin, with nuclear insertion involving multiple mechanisms including double-strand break repair associated with PR domain zinc-finger protein 9 (PRDM9) binding. The frequency of tumour-specific NUMTs differed between cancers, including a probably causal insertion in a myxoid liposarcoma. We found evidence of selection against NUMTs on the basis of size and genomic location, shaping a highly heterogenous and dynamic human NUMT landscape.}, } @article {pmid36183779, year = {2022}, author = {Moreno, ACR and Olean-Oliveira, A and Olean-Oliveira, T and Nunes, MT and Teixeira, MFS and Seraphim, PM}, title = {Resistance training prevents damage to the mitochondrial function of the skeletal muscle of rats exposed to secondary cigarette smoke.}, journal = {Life sciences}, volume = {309}, number = {}, pages = {121017}, doi = {10.1016/j.lfs.2022.121017}, pmid = {36183779}, issn = {1879-0631}, mesh = {Humans ; Rats ; Animals ; *Resistance Training ; *Cigarette Smoking ; Rats, Wistar ; Muscle, Skeletal/metabolism ; Mitochondria ; Tobacco/adverse effects ; Oxygen/metabolism ; Adenosine Triphosphate/metabolism ; }, abstract = {AIM: To analyze the consumption of oxygen and to quantify the mitochondrial respiratory chain proteins (OXPHOS) in the gastrocnemius muscle of rats exposed to cigarette smoke and/or RT practitioners.

MAIN METHODS: Wistar rats were divided into groups: Control (C), Smoker (S), Exercise (E) and Exercise Smoker (ES). Groups F and ES were exposed to the smoke of 4 cigarettes for 30 min, 2× a day, 5× a week, for 16 weeks. Groups E and ES performed four climbs with progressive load, 1× per day, 5× per week, for 16 weeks. The gastrocnemius muscle was collected for analysis of OXPHOS content and oxygen consumption. Groups S (vs. C) and ES (vs. C and E) showed lower body weight gain when observing the evolution curve.

KEY FINDINGS: The S rats showed a reduction in the NDUFB8 proteins of complex 1, SDHB of complex 2, MTC01 of complex 4 and ATP5A of complex 5 (ATP Synthase) compared to Group C. Additionally, S rats also showed increased consumption of O2 in Basal, Leak, Complex I and I/II combined measures compared to the other groups, suggesting that the activity of the mitochondria of these animals increased in terms of coupling and uncoupling parameters.

SIGNIFICANCE: Our data suggest that exposure to cigarette smoke for 16 weeks is capable of causing impairment of mitochondrial function with reduced expression of respiratory chain proteins in skeletal muscle. However, the RT was effective in preventing impairment of mitochondrial function in the skeletal muscle of rats exposed to secondary cigarette smoke.}, } @article {pmid36180833, year = {2022}, author = {Xiao, S and Xing, J and Nie, T and Su, A and Zhang, R and Zhao, Y and Song, W and Zhao, J}, title = {Comparative analysis of mitochondrial genomes of maize CMS-S subtypes provides new insights into male sterility stability.}, journal = {BMC plant biology}, volume = {22}, number = {1}, pages = {469}, pmid = {36180833}, issn = {1471-2229}, mesh = {*Genome, Mitochondrial/genetics ; Humans ; *Infertility, Male/genetics ; Male ; NADH Dehydrogenase/genetics ; Phylogeny ; Plant Infertility/genetics ; Zea mays/genetics ; }, abstract = {BACKGROUND: Cytoplasmic male sterility (CMS) is a trait of economic importance in the production of hybrid seeds. In CMS-S maize, exerted anthers appear frequently in florets of field-grown female populations where only complete male-sterile plants were expected. It has been reported that these reversions are associated with the loss of sterility-conferring regions or other rearrangements in the mitochondrial genome. However, the relationship between mitochondrial function and sterility stability is largely unknown.

RESULTS: In this study, we determined the ratio of plants carrying exerted anthers in the population of two CMS-S subtypes. The subtype with a high ratio of exerted anthers was designated as CMS-Sa, and the other with low ratio was designated as CMS-Sb. Through next-generation sequencing, we assembled and compared mitochondrial genomes of two CMS-S subtypes. Phylogenetic analyses revealed strong similarities between the two mitochondrial genomes. The sterility-associated regions, S plasmids, and terminal inverted repeats (TIRs) were intact in both genomes. The two subtypes maintained high transcript levels of the sterility gene orf355 in anther tissue. Most of the functional genes/proteins were identical at the nucleotide sequence and amino acid sequence levels in the two subtypes, except for NADH dehydrogenase subunit 1 (nad1). In the mitochondrial genome of CMS-Sb, a 3.3-kilobase sequence containing nad1-exon1 was absent from the second copy of the 17-kb repeat region. Consequently, we detected two copies of nad1-exon1 in CMS-Sa, but only one copy in CMS-Sb. During pollen development, nad1 transcription and mitochondrial biogenesis were induced in anthers of CMS-Sa, but not in those of CMS-Sb. We suggest that the impaired mitochondrial function in the anthers of CMS-Sb is associated with its more stable sterility.

CONCLUSIONS: Comprehensive analyses revealed diversity in terms of the copy number of the mitochondrial gene nad1-exon1 between two subtypes of CMS-S maize. This difference in copy number affected the transcript levels of nad1 and mitochondrial biogenesis in anther tissue, and affected the reversion rate of CMS-S maize. The results of this study suggest the involvement of mitochondrial robustness in modulation of sterility stability in CMS-S maize.}, } @article {pmid36158221, year = {2022}, author = {Ikeda, A and Imai, Y and Hattori, N}, title = {Neurodegeneration-associated mitochondrial proteins, CHCHD2 and CHCHD10-what distinguishes the two?.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {996061}, pmid = {36158221}, issn = {2296-634X}, abstract = {Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) and Coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) are mitochondrial proteins that are thought to be genes which duplicated during evolution and are the causative genes for Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal lobe dementia, respectively. CHCHD2 forms a heterodimer with CHCHD10 and a homodimer with itself, both of which work together within the mitochondria. Various pathogenic and disease-risk variants have been identified; however, how these mutations cause neurodegeneration in specific diseases remains a mystery. This review focuses on important new findings published since 2019 and discusses avenues to solve this mystery.}, } @article {pmid36143326, year = {2022}, author = {Govindharaj, GP and Babu, SB and Choudhary, JS and Asad, M and Chidambaranathan, P and Gadratagi, BG and Rath, PC and Naaz, N and Jaremko, M and Qureshi, KA and Kumar, U}, title = {Genome Organization and Comparative Evolutionary Mitochondriomics of Brown Planthopper, Nilaparvata lugens Biotype 4 Using Next Generation Sequencing (NGS).}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {36143326}, issn = {2075-1729}, abstract = {Nilaparvata lugens is the main rice pest in India. Until now, the Indian N. lugens mitochondrial genome has not been sequenced, which is a very important basis for population genetics and phylogenetic evolution studies. An attempt was made to sequence two examples of the whole mitochondrial genome of N. lugens biotype 4 from the Indian population for the first time. The mitogenomes of N. lugens are 16,072 and 16,081 bp long with 77.50% and 77.45% A + T contents, respectively, for both of the samples. The mitochondrial genome of N. lugens contains 37 genes, including 13 protein-coding genes (PCGs) (cox1-3, atp6, atp8, nad1-6, nad4l, and cob), 22 transfer RNA genes, and two ribosomal RNA (rrnS and rrnL) subunits genes, which are typical of metazoan mitogenomes. However, both samples of N. lugens mitogenome in the present study retained one extra copy of the trnC gene. Additionally, we also found 93 bp lengths for the atp8 gene in both of the samples, which were 60-70 bp less than that of the other sequenced mitogenomes of hemipteran insects. The phylogenetic analysis of the 19 delphacids mitogenome dataset yielded two identical topologies when rooted with Ugyops sp. in one clade, and the remaining species formed another clade with P. maidis and M. muiri being sisters to the remaining species. Further, the genus Nilaparvata formed a separate subclade with the other genera (Sogatella, Laodelphax, Changeondelphax, and Unkanodes) of Delphacidae. Additionally, the relationship among the biotypes of N. lugens was recovered as the present study samples (biotype-4) were separated from the three biotypes reported earlier. The present study provides the reference mitogenome for N. lugens biotype 4 that may be utilized for biotype differentiation and molecular-aspect-based future studies of N. lugens.}, } @article {pmid36115336, year = {2022}, author = {Giannakis, K and Arrowsmith, SJ and Richards, L and Gasparini, S and Chustecki, JM and Røyrvik, EC and Johnston, IG}, title = {Evolutionary inference across eukaryotes identifies universal features shaping organelle gene retention.}, journal = {Cell systems}, volume = {13}, number = {11}, pages = {874-884.e5}, doi = {10.1016/j.cels.2022.08.007}, pmid = {36115336}, issn = {2405-4720}, mesh = {*Eukaryota/genetics ; Bayes Theorem ; *Biological Evolution ; Plastids/genetics/metabolism ; Mitochondria/metabolism ; }, abstract = {Mitochondria and plastids power complex life. Why some genes and not others are retained in their organelle DNA (oDNA) genomes remains a debated question. Here, we attempt to identify the properties of genes and associated underlying mechanisms that determine oDNA retention. We harness over 15k oDNA sequences and over 300 whole genome sequences across eukaryotes with tools from structural biology, bioinformatics, machine learning, and Bayesian model selection. Previously hypothesized features, including the hydrophobicity of a protein product, and less well-known features, including binding energy centrality within a protein complex, predict oDNA retention across eukaryotes, with additional influences of nucleic acid and amino acid biochemistry. Notably, the same features predict retention in both organelles, and retention models learned from one organelle type quantitatively predict retention in the other, supporting the universality of these features-which also distinguish gene profiles in more recent, independent endosymbiotic relationships. A record of this paper's transparent peer review process is included in the supplemental information.}, } @article {pmid36107771, year = {2022}, author = {Lesch, E and Schilling, MT and Brenner, S and Yang, Y and Gruss, OJ and Knoop, V and Schallenberg-Rüdinger, M}, title = {Plant mitochondrial RNA editing factors can perform targeted C-to-U editing of nuclear transcripts in human cells.}, journal = {Nucleic acids research}, volume = {50}, number = {17}, pages = {9966-9983}, pmid = {36107771}, issn = {1362-4962}, mesh = {Amino Acids ; Cytidine ; Humans ; *Plant Proteins/genetics ; RNA/genetics ; RNA, Mitochondrial/genetics ; RNA, Plant/genetics ; *RNA-Binding Proteins/genetics/metabolism ; Uridine/genetics ; }, abstract = {RNA editing processes are strikingly different in animals and plants. Up to thousands of specific cytidines are converted into uridines in plant chloroplasts and mitochondria whereas up to millions of adenosines are converted into inosines in animal nucleo-cytosolic RNAs. It is unknown whether these two different RNA editing machineries are mutually incompatible. RNA-binding pentatricopeptide repeat (PPR) proteins are the key factors of plant organelle cytidine-to-uridine RNA editing. The complete absence of PPR mediated editing of cytosolic RNAs might be due to a yet unknown barrier that prevents its activity in the cytosol. Here, we transferred two plant mitochondrial PPR-type editing factors into human cell lines to explore whether they could operate in the nucleo-cytosolic environment. PPR56 and PPR65 not only faithfully edited their native, co-transcribed targets but also different sets of off-targets in the human background transcriptome. More than 900 of such off-targets with editing efficiencies up to 91%, largely explained by known PPR-RNA binding properties, were identified for PPR56. Engineering two crucial amino acid positions in its PPR array led to predictable shifts in target recognition. We conclude that plant PPR editing factors can operate in the entirely different genetic environment of the human nucleo-cytosol and can be intentionally re-engineered towards new targets.}, } @article {pmid36101314, year = {2022}, author = {Zhou, S and He, LI and Ma, S and Xu, S and Zhai, Q and Guan, P and Wang, H and Shi, J}, title = {Taxonomic status of Rana nigromaculata mongolia and the validity of Pelophylax tenggerensis (Anura, Ranidae).}, journal = {Zootaxa}, volume = {5165}, number = {4}, pages = {486-500}, doi = {10.11646/zootaxa.5165.4.2}, pmid = {36101314}, issn = {1175-5334}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Mongolia ; Phylogeny ; *Ranidae/genetics ; }, abstract = {The Black-spotted Pond Frog, Pelophylax nigromaculatus, is widely distributed across mainland China, Korean Peninsula, and Japan. The taxonomic relationships among P. n. nigromaculatus, Rana nigromaculata mongolia (sensu P. n. mongolicus), and P. tenggerensis have long been ambiguous. Here we examine the topotype specimens of P. tenggerensis and R. n. mongolia, and provide phylogenic analyses based on four mitochondrial DNA sequences. The combined evidences from morphology and molecular phylogeny have shown the distinct specific-level of P. n. mongolicus that distant from P. nigromaculatus, while indicating the homogeneity between P. n. mongolicus and P. tenggerensis. Thus, we suggest elevating P. n. mongolicus as a full species Pelophylax mongolicus comb. nov., and place P. tenggerensis to be a secondary synonym of P. mongolicus comb. nov.}, } @article {pmid36097126, year = {2022}, author = {Joshi, BD and Kumar, V and De, R and Sharma, R and Bhattacharya, A and Dolker, S and Pal, R and Kumar, VP and Sathyakumar, S and Adhikari, BS and Habib, B and Goyal, SP}, title = {Mitochondrial cytochrome b indicates the presence of two paraphyletic diverged lineages of the blue sheep Pseudois nayaur across the Indian Himalaya: conservation implications.}, journal = {Molecular biology reports}, volume = {49}, number = {11}, pages = {11177-11186}, pmid = {36097126}, issn = {1573-4978}, mesh = {Animals ; *Cytochromes b/genetics ; *Genetics, Population ; Haplotypes/genetics ; Phylogeny ; Phylogeography ; Sheep/genetics ; *Mitochondria/metabolism ; }, abstract = {BACKGROUND: Populations exhibit signatures of local adaptive traits due to spatial and environmental heterogeneity resulting in microevolution. The blue sheep is widely distributed across the high Asian mountains and are the snow leopard's principal prey species. These mountains differ in their evolutionary history due to differential glaciation and deglaciation periods, orography, and rainfall patterns, and such factors causes diversification in species.

METHODS AND RESULTS: Therefore, we assess the phylogeographic status of blue sheep using the mitochondrial cytochrome b gene (220 bp) across the Indian Himalayan region (IHR) and its relationship with other populations. Of the observed five haplotypes, two and three were from the western Himalayas (WH) and eastern Himalayas (EH) respectively. One of the haplotypes from WH was shared with the population of Pamir plateau, suggesting historical maternal connectivity between these areas. The phylogenetic analyses split the blue sheep into two paraphyletic clades, and western and eastern populations of IHR were within the Pamir and Tibetan plateau clades, respectively. We observed a relatively higher mean sequence divergence in the EH population than in the WH.

CONCLUSION: We propose five 'Evolutionary Significant Units' across the blue sheep distribution range based on observed variation in the species' ecological requirements, orography, climatic conditions, and maternal lineages, viz.; Western Himalaya-Pamir plateau (WHPP); Eastern Himalaya-Tibetan plateau (EHTP); Qilian mountains; Helan mountains and Hengduan mountains population. Despite the small sample size, population divergence was observed across the IHR, therefore, we suggest a transboundary, collaborative study on comparative morphology, anatomy, ecology, behaviour, and population genetics using harmonized different genetic markers for identifying the overall taxonomic status of the blue sheep across its range for planning effective conservation strategies.}, } @article {pmid36085554, year = {2022}, author = {Jacquat, AG and Ulla, SB and Debat, HJ and Muñoz-Adalia, EJ and Theumer, MG and Pedrajas, MDG and Dambolena, JS}, title = {An in silico analysis revealed a novel evolutionary lineage of putative mitoviruses.}, journal = {Environmental microbiology}, volume = {24}, number = {12}, pages = {6463-6475}, doi = {10.1111/1462-2920.16202}, pmid = {36085554}, issn = {1462-2920}, mesh = {Phylogeny ; *RNA Viruses/genetics ; Mitochondria/genetics ; Genome, Viral ; Plant Diseases/microbiology ; RNA, Viral ; }, abstract = {Mitoviruses (family Mitoviridae) are small capsid-less RNA viruses that replicate in the mitochondria of fungi and plants. However, to date, the only authentic animal mitovirus infecting an insect was identified as Lutzomyia longipalpis mitovirus 1 (LulMV1). Public databases of transcriptomic studies from several animals may be a good source for identifying the often missed mitoviruses. Consequently, a search of mitovirus-like transcripts at the NCBI transcriptome shotgun assembly (TSA) library, and a search for the mitoviruses previously recorded at the NCBI non-redundant (nr) protein sequences library, were performed in order to identify new mitovirus-like sequences associated with animals. In total, 10 new putative mitoviruses were identified in the TSA database and 8 putative mitoviruses in the nr protein database. To our knowledge, these results represent the first evidence of putative mitoviruses associated with poriferan, cnidarians, echinoderms, crustaceans, myriapods and arachnids. According to different phylogenetic inferences using the maximum likelihood method, these 18 putative mitoviruses form a robust monophyletic lineage with LulMV1, the only known animal-infecting mitovirus. These findings based on in silico procedures provide strong evidence for the existence of a clade of putative mitoviruses associated with animals, which has been provisionally named 'kvinmitovirus'.}, } @article {pmid36083897, year = {2022}, author = {Ba, Q and Hei, Y and Dighe, A and Li, W and Maziarz, J and Pak, I and Wang, S and Wagner, GP and Liu, Y}, title = {Proteotype coevolution and quantitative diversity across 11 mammalian species.}, journal = {Science advances}, volume = {8}, number = {36}, pages = {eabn0756}, pmid = {36083897}, issn = {2375-2548}, support = {P50 CA196530/CA/NCI NIH HHS/United States ; R01 GM137031/GM/NIGMS NIH HHS/United States ; U54 CA209992/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Gene Expression Profiling ; *Mammals/genetics/metabolism ; Proteome/metabolism ; *Proteomics ; Transcriptome ; }, abstract = {Evolutionary profiling has been largely limited to the nucleotide level. Using consistent proteomic methods, we quantified proteomic and phosphoproteomic layers in fibroblasts from 11 common mammalian species, with transcriptomes as reference. Covariation analysis indicates that transcript and protein expression levels and variabilities across mammals remarkably follow functional role, with extracellular matrix-associated expression being the most variable, demonstrating strong transcriptome-proteome coevolution. The biological variability of gene expression is universal at both interindividual and interspecies scales but to a different extent. RNA metabolic processes particularly show higher interspecies versus interindividual variation. Our results further indicate that while the ubiquitin-proteasome system is strongly conserved in mammals, lysosome-mediated protein degradation exhibits remarkable variation between mammalian lineages. In addition, the phosphosite profiles reveal a phosphorylation coevolution network independent of protein abundance.}, } @article {pmid36083445, year = {2022}, author = {Wang, S and Luo, H}, title = {Estimating the Divergence Times of Alphaproteobacteria Based on Mitochondrial Endosymbiosis and Eukaryotic Fossils.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2569}, number = {}, pages = {95-116}, pmid = {36083445}, issn = {1940-6029}, mesh = {*Alphaproteobacteria/genetics ; Eukaryota ; Evolution, Molecular ; Fossils ; Mitochondria/genetics ; Phylogeny ; Symbiosis/genetics ; }, abstract = {Alphaproteobacteria is one of the most abundant bacterial lineages that successfully colonize diverse marine and terrestrial environments on Earth. In addition, many alphaproteobacterial lineages have established close association with eukaryotes. This makes Alphaproteobacteria a promising system to test the link between the emergence of ecologically important bacteria and related geological events and the co-evolution between symbiotic bacteria and their hosts. Understanding the timescale of evolution of Alphaproteobacteria is key to testing these hypotheses, which is limited by the scarcity of bacterial fossils, however. Based on the mitochondrial endosymbiosis which posits that the mitochondrion originated from an alphaproteobacterial lineage, we propose a new strategy to estimate the divergence times of lineages within the Alphaproteobacteria by leveraging the fossil records of eukaryotes. In this chapter, we describe the workflow of the mitochondria-based method to date Alphaproteobacteria evolution by detailing the software, methods, and commands used for each step. Visualization of data and results is also described. We also provide related notes with background information and alternative options. All codes used to build this protocol are made available to the public, and we strive to make this protocol user-friendly in particular to microbiologists with limited practical skills in bioinformatics.}, } @article {pmid36071602, year = {2022}, author = {Zhang, M and Zhang, C and Hu, P and Shi, L and Ju, M and Zhang, B and Li, X and Han, X and Wang, K and Li, X and Qiao, R}, title = {Comprehensive analysis of mitogenome of native Henan pig breeds with 58 worldwide pig breeds.}, journal = {Animal genetics}, volume = {53}, number = {6}, pages = {803-813}, doi = {10.1111/age.13261}, pmid = {36071602}, issn = {1365-2052}, mesh = {Animals ; DNA, Mitochondrial/genetics ; Genetic Variation ; *Genome, Mitochondrial ; Haplotypes ; Phylogeny ; Swine/genetics ; }, abstract = {Mitochondria follow non-Mendelian maternal inheritance, and thus can be used to compare genetic diversity and infer the expansion and migration between animal populations. Based on the mitochondrial DNA sequences of 58 pig breeds from Asia, Europe, Oceania, and America, we observed a distinct division of Eurasian pig species into two main Haplogroups (A and B), with the exception of the Berkshire and Yorkshire breeds. Oceanian pigs were much more similar to European and American pigs in Haplogroup A. Additionally, native Chinese pigs exhibited the most abundant genetic polymorphisms and occupied the centre of Haplogroup B. Miyazaki (Japan) and Siberia (Russia) are two distant and disconnected regions; however, most pigs from these regions were clustered into a subcluster, while native pigs from Korea clustered into a second subcluster. This study is the first to report that pigs from Thailand and Vietnam had haplotypes similar to those of Henan, where the earliest evidence of domestic pigs was found from the Yellow River Basin of North China. Local Henan pig breeds are related to many Asian breeds while still having their own mutation identity, such as g.314 delins T>AC/AT/C of the 12S rRNA gene in Yuxi. Some pigs from Palawan, Itbayat, and Batan Islands of the Philippines and Lanyu Island of China were distinct from other Asian pigs and clustered together into Haplogroup C. These findings show that the complexity of domestication of worldwide pig breeds and mitochondria could reflect genetic communication between pig breeds due to geographical proximity and human activities.}, } @article {pmid36055768, year = {2022}, author = {Khan, K and Van Aken, O}, title = {The colonization of land was a likely driving force for the evolution of mitochondrial retrograde signalling in plants.}, journal = {Journal of experimental botany}, volume = {73}, number = {21}, pages = {7182-7197}, pmid = {36055768}, issn = {1460-2431}, mesh = {*Signal Transduction ; Seeds ; Mitochondria ; Eukaryota ; Cyclin-Dependent Kinases ; *Arabidopsis/genetics ; Transcription Factors/genetics ; }, abstract = {Most retrograde signalling research in plants was performed using Arabidopsis, so an evolutionary perspective on mitochondrial retrograde regulation (MRR) is largely missing. Here, we used phylogenetics to track the evolutionary origins of factors involved in plant MRR. In all cases, the gene families can be traced to ancestral green algae or earlier. However, the specific subfamilies containing factors involved in plant MRR in many cases arose during the transition to land. NAC transcription factors with C-terminal transmembrane domains, as observed in the key regulator ANAC017, can first be observed in non-vascular mosses, and close homologs to ANAC017 can be found in seed plants. Cyclin-dependent kinases (CDKs) are common to eukaryotes, but E-type CDKs that control MRR also diverged in conjunction with plant colonization of land. AtWRKY15 can be traced to the earliest land plants, while AtWRKY40 only arose in angiosperms and AtWRKY63 even more recently in Brassicaceae. Apetala 2 (AP2) transcription factors are traceable to algae, but the ABI4 type again only appeared in seed plants. This strongly suggests that the transition to land was a major driver for developing plant MRR pathways, while additional fine-tuning events have appeared in seed plants or later. Finally, we discuss how MRR may have contributed to meeting the specific challenges that early land plants faced during terrestrialization.}, } @article {pmid36045215, year = {2022}, author = {Monsanto, DM and Main, DC and Janion-Scheepers, C and Emami-Khoyi, A and Deharveng, L and Bedos, A and Potapov, M and Parbhu, SP and Le Roux, JJ and Teske, PR and van Vuuren, BJ}, title = {Mitogenome selection in the evolution of key ecological strategies in the ancient hexapod class Collembola.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {14810}, pmid = {36045215}, issn = {2045-2322}, mesh = {Animals ; *Arthropods/genetics/metabolism ; Evolution, Molecular ; Fossils ; Genes, Mitochondrial ; *Genome, Mitochondrial ; Insecta/genetics ; Phylogeny ; }, abstract = {A longstanding question in evolutionary biology is how natural selection and environmental pressures shape the mitochondrial genomic architectures of organisms. Mitochondria play a pivotal role in cellular respiration and aerobic metabolism, making their genomes functionally highly constrained. Evaluating selective pressures on mitochondrial genes can provide functional and ecological insights into the evolution of organisms. Collembola (springtails) are an ancient hexapod group that includes the oldest terrestrial arthropods in the fossil record, and that are closely associated with soil environments. Of interest is the diversity of habitat stratification preferences (life forms) exhibited by different species within the group. To understand whether signals of positive selection are linked to the evolution of life forms, we analysed 32 published Collembola mitogenomes in a phylomitogenomic framework. We found no evidence that signatures of selection are correlated with the evolution of novel life forms, but rather that mutations have accumulated as a function of time. Our results highlight the importance of nuclear-mitochondrial interactions in the evolution of collembolan life forms and that mitochondrial genomic data should be interpreted with caution, as complex selection signals may complicate evolutionary inferences.}, } @article {pmid36042193, year = {2022}, author = {Kuhle, B and Hirschi, M and Doerfel, LK and Lander, GC and Schimmel, P}, title = {Structural basis for shape-selective recognition and aminoacylation of a D-armless human mitochondrial tRNA.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {5100}, pmid = {36042193}, issn = {2041-1723}, support = {R01 GM125908/GM/NIGMS NIH HHS/United States ; S10 OD021634/OD/NIH HHS/United States ; }, mesh = {*Amino Acyl-tRNA Synthetases/metabolism ; Aminoacylation/genetics ; Animals ; Humans ; Mammals/genetics ; Mitochondria/metabolism ; RNA, Mitochondrial/metabolism ; *RNA, Transfer/genetics/metabolism ; }, abstract = {Human mitochondrial gene expression relies on the specific recognition and aminoacylation of mitochondrial tRNAs (mtRNAs) by nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs). Despite their essential role in cellular energy homeostasis, strong mutation pressure and genetic drift have led to an unparalleled sequence erosion of animal mtRNAs. The structural and functional consequences of this erosion are not understood. Here, we present cryo-EM structures of the human mitochondrial seryl-tRNA synthetase (mSerRS) in complex with mtRNA[Ser(GCU)]. These structures reveal a unique mechanism of substrate recognition and aminoacylation. The mtRNA[Ser(GCU)] is highly degenerated, having lost the entire D-arm, tertiary core, and stable L-shaped fold that define canonical tRNAs. Instead, mtRNA[Ser(GCU)] evolved unique structural innovations, including a radically altered T-arm topology that serves as critical identity determinant in an unusual shape-selective readout mechanism by mSerRS. Our results provide a molecular framework to understand the principles of mito-nuclear co-evolution and specialized mechanisms of tRNA recognition in mammalian mitochondrial gene expression.}, } @article {pmid36010594, year = {2022}, author = {Liu, Y and Chen, C and Wang, X and Sun, Y and Zhang, J and Chen, J and Shi, Y}, title = {An Epigenetic Role of Mitochondria in Cancer.}, journal = {Cells}, volume = {11}, number = {16}, pages = {}, pmid = {36010594}, issn = {2073-4409}, mesh = {Carcinogenesis/genetics/metabolism ; *Epigenesis, Genetic ; Histones/metabolism ; Humans ; Mitochondria/genetics/metabolism ; *Neoplasms/genetics/metabolism ; Tumor Microenvironment ; }, abstract = {Mitochondria are not only the main energy supplier but are also the cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD[+], and O-linked beta-N-acetylglucosamine (O-GlcNAc), which are the main substrates for DNA methylation and histone post-translation modifications, essential for gene transcriptional regulation and cell fate determination. Tumorigenesis is attributed to many factors, including gene mutations and tumor microenvironment. Mitochondria and epigenetics play essential roles in tumor initiation, evolution, metastasis, and recurrence. Targeting mitochondrial metabolism and epigenetics are promising therapeutic strategies for tumor treatment. In this review, we summarize the roles of mitochondria in key metabolites required for epigenetics modification and in cell fate regulation and discuss the current strategy in cancer therapies via targeting epigenetic modifiers and related enzymes in metabolic regulation. This review is an important contribution to the understanding of the current metabolic-epigenetic-tumorigenesis concept.}, } @article {pmid36009607, year = {2022}, author = {Wu, L and Tong, Y and Ayivi, SPG and Storey, KB and Zhang, JY and Yu, DN}, title = {The Complete Mitochondrial Genomes of Three Sphenomorphinae Species (Squamata: Scincidae) and the Selective Pressure Analysis on Mitochondrial Genomes of Limbless Isopachys gyldenstolpei.}, journal = {Animals : an open access journal from MDPI}, volume = {12}, number = {16}, pages = {}, pmid = {36009607}, issn = {2076-2615}, abstract = {In order to adapt to diverse habitats, organisms often evolve corresponding adaptive mechanisms to cope with their survival needs. The species-rich family of Scincidae contains both limbed and limbless species, which differ fundamentally in their locomotor demands, such as relying on the movement of limbs or only body swing to move. Locomotion requires energy, and different types of locomotion have their own energy requirements. Mitochondria are the energy factories of living things, which provide a lot of energy for various physiological activities of organisms. Therefore, mitochondrial genomes could be tools to explore whether the limb loss of skinks are selected by adaptive evolution. Isopachys gyldenstolpei is a typical limbless skink. Here, we report the complete mitochondrial genomes of I. gyldenstolpei, Sphenomorphus indicus, and Tropidophorus hainanus. The latter two species were included as limbed comparator species to the limbless I. gyldenstolpei. The results showed that the full lengths of the mitochondrial genomes of I. gyldenstolpei, S. indicus, and T. hainanus were 17,210, 16,944, and 17,001 bp, respectively. Three mitochondrial genomes have typical circular double-stranded structures similar to other reptiles, including 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and the control region. Three mitochondrial genomes obtained in this study were combined with fifteen mitochondrially complete genomes of Scincidae in the NCBI database; the phylogenetic relationship between limbless I. gyldenstolpei and limbed skinks (S. indicus and T. hainanus) is discussed. Through BI and ML trees, Sphenomorphinae and Mabuyinae were monophyletic, while the paraphyly of Scincinae was also recovered. The limbless skink I. gyldenstolpei is closer to the species of Tropidophorus, which has formed a sister group with (T. hainanus + T. hangman). In the mitochondrial genome adaptations between limbless I. gyldenstolpei and limbed skinks, one positively selected site was found in the branch-site model analysis, which was located in ND2 (at position 28, BEB value = 0.907). Through analyzing the protein structure and function of the selected site, we found it was distributed in mitochondrial protein complex I. Positive selection of some mitochondrial genes in limbless skinks may be related to the requirement of energy to fit in their locomotion. Further research is still needed to confirm this conclusion though.}, } @article {pmid35998817, year = {2022}, author = {Franzolin, GN and Araújo, BL and Zatti, SA and Naldoni, J and Adriano, EA}, title = {Occurrence of the host-parasite system Rhaphiodon vulpinus and Ceratomyxa barbata n. sp. in the two largest watersheds in South America.}, journal = {Parasitology international}, volume = {91}, number = {}, pages = {102651}, doi = {10.1016/j.parint.2022.102651}, pmid = {35998817}, issn = {1873-0329}, mesh = {Animals ; DNA, Ribosomal/genetics ; *Fish Diseases/epidemiology/parasitology ; Fishes ; Gallbladder/parasitology ; *Myxozoa ; *Parasites/genetics ; *Parasitic Diseases, Animal/parasitology ; Phylogeny ; }, abstract = {While around world, species of the genus Ceratomyxa parasite majority marine hosts, growing diversity has been reported in South American freshwater fish. The present study reports Ceratomyxa barbata n. sp. parasitizing the gallbladder of the Rhaphiodon vulpinus fish from the Amazon and La Plata basins. Morphological (light and transmission electron microscopy), molecular (sequencing of small subunit ribosomal DNA - SSU rDNA), and phylogenetic analyses were used to characterize the new species. Worm-like plasmodia endowed with motility were found swimming freely in the bile. The myxospores were elongated, lightly arcuate, with rounded ends and had polar tubules with 3 coils in the polar capsules. Ultrastructural analysis revealed plasmodia composed of an outer cytoplasmic region, where elongated tubular mitochondria, a rough endoplasmic reticulum, sporogonic stages, and a large vacuole occupying the internal area were observed. Phylogenetic analysis, based on SSU rDNA, found that among all South America freshwater Ceratomyxa species, C. barbata n. sp. arises as an earlier divergent species. The present study reveals the occurrence of this host-parasite system (R. vulpinus/C. barbata n. sp.) in the two largest watersheds on the continent.}, } @article {pmid35997667, year = {2022}, author = {Hirakawa, Y and Hanawa, Y and Yoneda, K and Suzuki, I}, title = {Evolution of a chimeric mitochondrial carbonic anhydrase through gene fusion in a haptophyte alga.}, journal = {FEBS letters}, volume = {596}, number = {23}, pages = {3051-3059}, doi = {10.1002/1873-3468.14475}, pmid = {35997667}, issn = {1873-3468}, mesh = {*Haptophyta/genetics/metabolism ; *Carbonic Anhydrases/genetics/metabolism ; Plants/metabolism ; Carbon Dioxide/metabolism ; Recombinant Proteins/genetics ; Gene Fusion ; }, abstract = {Carbonic anhydrases (CAs) are a universal enzyme family that catalyses the interconversion of carbon dioxide and bicarbonate, and they are localized in most compartments including mitochondria and plastids. Thus far, eight classes of CAs (α-, β-, γ-, δ-, ζ-, η-, θ- and ι-CA) have been characterized. This study reports an interesting gene encoding a fusion protein of β-CA and ι-CA found in the haptophyte Isochrysis galbana. Recombinant protein assays demonstrated that the C-terminal ι-CA region catalyses CO2 hydration, whereas the N-terminal β-CA region no longer exhibits enzymatic activity. Considering that haptophytes generally have mitochondrion-localized β-CAs and plastid-localized ι-CAs, the fusion CA would show an intermediate stage in which mitochondrial β-CA is replaced by ι-CA in a haptophyte species.}, } @article {pmid35978085, year = {2022}, author = {Yue, J and Lu, Q and Ni, Y and Chen, P and Liu, C}, title = {Comparative analysis of the plastid and mitochondrial genomes of Artemisia giraldii Pamp.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {13931}, pmid = {35978085}, issn = {2045-2322}, mesh = {*Artemisia/genetics ; Evolution, Molecular ; *Genome, Mitochondrial ; *Genome, Plastid ; Pathogen-Associated Molecular Pattern Molecules ; Phylogeny ; Plastids/genetics ; }, abstract = {Artemisia giraldii Pamp. is an herbaceous plant distributed only in some areas in China. To understand the evolutionary relationship between plastid and mitochondria in A. giraldii, we sequenced and analysed the plastome and mitogenome of A. giraldii on the basis of Illumina and Nanopore DNA sequencing data. The mitogenome was 194,298 bp long, and the plastome was 151,072 bp long. The mitogenome encoded 56 genes, and the overall GC content was 45.66%. Phylogenetic analysis of the two organelle genomes revealed that A. giraldii is located in the same branching position. We found 13 pairs of homologous sequences between the plastome and mitogenome, and only one of them might have transferred from the plastid to the mitochondria. Gene selection pressure analysis in the mitogenome showed that ccmFc, nad1, nad6, atp9, atp1 and rps12 may undergo positive selection. According to the 18 available plastome sequences, we found 17 variant sites in two hypervariable regions that can be used in completely distinguishing 18 Artemisia species. The most interesting discovery was that the mitogenome of A. giraldii was only 43,226 bp larger than the plastome. To the best of our knowledge, this study represented one of the smallest differences between all sequenced mitogenomes and plastomes from vascular plants. The above results can provide a reference for future taxonomic and molecular evolution studies of Asteraceae species.}, } @article {pmid35973607, year = {2022}, author = {Holt, AG and Davies, AM}, title = {A comparison of mtDNA deletion mutant proliferation mechanisms.}, journal = {Journal of theoretical biology}, volume = {551-552}, number = {}, pages = {111244}, doi = {10.1016/j.jtbi.2022.111244}, pmid = {35973607}, issn = {1095-8541}, mesh = {Cell Proliferation/genetics ; Clone Cells ; *DNA, Mitochondrial/genetics ; Humans ; *Mitochondria/genetics ; Mutation ; Mutation Rate ; }, abstract = {In this paper we use simulation methods to investigate the proliferation of deletion mutations of mitochondrial DNA in neurons. We simulate three mtDNA proliferation mechanisms, namely, random drift, replicative advantage and vicious cycle. For each mechanism, we investigated the effect mutation rates have on neuron loss within a human host. We also compare heteroplasmy of each mechanism at mutation rates that yield the levels neuron loss that would be associated with dementia. Both random drift and vicious cycle predicted high levels of heteroplasmy, while replicative advantage showed a small number of dominant clones with a low background of heteroplasmy.}, } @article {pmid35957532, year = {2022}, author = {Wang, G and Wang, Y and Ni, J and Li, R and Zhu, F and Wang, R and Tian, Q and Shen, Q and Yang, Q and Tang, J and Murcha, MW and Wang, G}, title = {An MCIA-like complex is required for mitochondrial complex I assembly and seed development in maize.}, journal = {Molecular plant}, volume = {15}, number = {9}, pages = {1470-1487}, doi = {10.1016/j.molp.2022.08.001}, pmid = {35957532}, issn = {1752-9867}, mesh = {Cell Nucleus/metabolism ; *Electron Transport Complex I/genetics/metabolism ; Humans ; Mitochondria/metabolism ; Mitochondrial Proteins/genetics/metabolism ; Seeds/metabolism ; *Zea mays/metabolism ; }, abstract = {During adaptive radiation, mitochondria have co-evolved with their hosts, leading to gain or loss of subunits and assembly factors of respiratory complexes. Plant mitochondrial complex I harbors ∼40 nuclear- and 9 mitochondrial-encoded subunits, and is formed by stepwise assembly during which different intermediates are integrated via various assembly factors. In mammals, the mitochondrial complex I intermediate assembly (MCIA) complex is required for building the membrane arm module. However, plants have lost almost all of the MCIA complex components, giving rise to the hypothesis that plants follow an ancestral pathway to assemble the membrane arm subunits. Here, we characterize a maize crumpled seed mutant, crk1, and reveal by map-based cloning that CRK1 encodes an ortholog of human complex I assembly factor 1, zNDUFAF1, the only evolutionarily conserved MCIA subunit in plants. zNDUFAF1 is localized in the mitochondria and accumulates in two intermediate complexes that contain complex I membrane arm subunits. Disruption of zNDUFAF1 results in severe defects in complex I assembly and activity, a cellular bioenergetic shift to aerobic glycolysis, and mitochondrial vacuolation. Moreover, we found that zNDUFAF1, the putative mitochondrial import inner membrane translocase ZmTIM17-1, and the isovaleryl-coenzyme A dehydrogenase ZmIVD1 interact each other, and could be co-precipitated from the mitochondria and co-migrate in the same assembly intermediates. Knockout of either ZmTIM17-1 or ZmIVD1 could lead to the significantly reduced complex I stability and activity as well as defective seeds. These results suggest that zNDUFAF1, ZmTIM17-1 and ZmIVD1 probably form an MCIA-like complex that is essential for the biogenesis of mitochondrial complex I and seed development in maize. Our findings also imply that plants and mammals recruit MCIA subunits independently for mitochondrial complex I assembly, highlighting the importance of parallel evolution in mitochondria adaptation to their hosts.}, } @article {pmid35955668, year = {2022}, author = {Manousaki, A and Bagnall, J and Spiller, D and Balarezo-Cisneros, LN and White, M and Delneri, D}, title = {Quantitative Characterisation of Low Abundant Yeast Mitochondrial Proteins Reveals Compensation for Haplo-Insufficiency in Different Environments.}, journal = {International journal of molecular sciences}, volume = {23}, number = {15}, pages = {}, pmid = {35955668}, issn = {1422-0067}, support = {BB/M011208/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/T002123/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; GTP Phosphohydrolases/metabolism ; Membrane Proteins/metabolism ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; *Saccharomyces cerevisiae/metabolism ; *Saccharomyces cerevisiae Proteins/metabolism ; }, abstract = {The quantification of low abundant membrane-binding proteins such as transcriptional factors and chaperones has proven difficult, even with the most sophisticated analytical technologies. Here, we exploit and optimise the non-invasive Fluorescence Correlation Spectroscopy (FCS) for the quantitation of low abundance proteins, and as proof of principle, we choose two interacting proteins involved in the fission of mitochondria in yeast, Fis1p and Mdv1p. In Saccharomyces cerevisiae, the recruitment of Fis1p and Mdv1p to mitochondria is essential for the scission of the organelles and the retention of functional mitochondrial structures in the cell. We use FCS in single GFP-labelled live yeast cells to quantify the protein abundance in homozygote and heterozygote cells and to investigate the impact of the environments on protein copy number, bound/unbound protein state and mobility kinetics. Both proteins were observed to localise predominantly at mitochondrial structures, with the Mdv1p bound state increasing significantly in a strictly respiratory environment. Moreover, a compensatory mechanism that controls Fis1p abundance upon deletion of one allele was observed in Fis1p but not in Mdv1p, suggesting differential regulation of Fis1p and Mdv1p protein expression.}, } @article {pmid35931723, year = {2022}, author = {Silva, NM and Kreutzer, S and Souleles, A and Triantaphyllou, S and Kotsakis, K and Urem-Kotsou, D and Halstead, P and Efstratiou, N and Kotsos, S and Karamitrou-Mentessidi, G and Adaktylou, F and Chondroyianni-Metoki, A and Pappa, M and Ziota, C and Sampson, A and Papathanasiou, A and Vitelli, K and Cullen, T and Kyparissi-Apostolika, N and Lanz, AZ and Peters, J and Rio, J and Wegmann, D and Burger, J and Currat, M and Papageorgopoulou, C}, title = {Ancient mitochondrial diversity reveals population homogeneity in Neolithic Greece and identifies population dynamics along the Danubian expansion axis.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {13474}, pmid = {35931723}, issn = {2045-2322}, support = {31003A_156853/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Bayes Theorem ; DNA, Ancient ; *DNA, Mitochondrial/genetics ; Europe ; Genetics, Population ; Greece ; History, Ancient ; Humans ; *Mitochondria/genetics ; Population Dynamics ; }, abstract = {The aim of the study is to investigate mitochondrial diversity in Neolithic Greece and its relation to hunter-gatherers and farmers who populated the Danubian Neolithic expansion axis. We sequenced 42 mitochondrial palaeogenomes from Greece and analysed them together with European set of 328 mtDNA sequences dating from the Early to the Final Neolithic and 319 modern sequences. To test for population continuity through time in Greece, we use an original structured population continuity test that simulates DNA from different periods by explicitly considering the spatial and temporal dynamics of populations. We explore specific scenarios of the mode and tempo of the European Neolithic expansion along the Danubian axis applying spatially explicit simulations coupled with Approximate Bayesian Computation. We observe a striking genetic homogeneity for the maternal line throughout the Neolithic in Greece whereas population continuity is rejected between the Neolithic and present-day Greeks. Along the Danubian expansion axis, our best-fitting scenario supports a substantial decrease in mobility and an increasing local hunter-gatherer contribution to the gene-pool of farmers following the initial rapid Neolithic expansion. Οur original simulation approach models key demographic parameters rather than inferring them from fragmentary data leading to a better understanding of this important process in European prehistory.}, } @article {pmid35920138, year = {2022}, author = {Liao, T and Wang, S and Stüeken, EE and Luo, H}, title = {Phylogenomic Evidence for the Origin of Obligate Anaerobic Anammox Bacteria Around the Great Oxidation Event.}, journal = {Molecular biology and evolution}, volume = {39}, number = {8}, pages = {}, pmid = {35920138}, issn = {1537-1719}, mesh = {*Ammonium Compounds ; Anaerobic Ammonia Oxidation ; Anaerobiosis ; Bacteria/genetics ; *Bacteria, Anaerobic/genetics ; Nitrites ; Nitrogen ; Oxidation-Reduction ; Phylogeny ; Quaternary Ammonium Compounds ; }, abstract = {The anaerobic ammonium oxidation (anammox) bacteria can transform ammonium and nitrite to dinitrogen gas, and this obligate anaerobic process accounts for up to half of the global nitrogen loss in surface environments. Yet its origin and evolution, which may give important insights into the biogeochemistry of early Earth, remain enigmatic. Here, we performed a comprehensive phylogenomic and molecular clock analysis of anammox bacteria within the phylum Planctomycetes. After accommodating the uncertainties and factors influencing time estimates, which include implementing both a traditional cyanobacteria-based and a recently developed mitochondria-based molecular dating approach, we estimated a consistent origin of anammox bacteria at early Proterozoic and most likely around the so-called Great Oxidation Event (GOE; 2.32-2.5 Ga) which fundamentally changed global biogeochemical cycles. We further showed that during the origin of anammox bacteria, genes involved in oxidative stress adaptation, bioenergetics, and anammox granules formation were recruited, which might have contributed to their survival on an increasingly oxic Earth. Our findings suggest the rising levels of atmospheric oxygen, which made nitrite increasingly available, was a potential driving force for the emergence of anammox bacteria. This is one of the first studies that link the GOE to the evolution of obligate anaerobic bacteria.}, } @article {pmid35920046, year = {2022}, author = {Paulino, MG and Rossi, PA and Venturini, FP and Tavares, D and Sakuragui, MM and Moraes, G and Terezan, AP and Fernandes, JB and Giani, A and Fernandes, MN}, title = {Liver dysfunction and energy storage mobilization in traíra, Hoplias malabaricus (Teleostei, Erythrinidae) induced by subchronic exposure to toxic cyanobacterial crude extract.}, journal = {Environmental toxicology}, volume = {37}, number = {11}, pages = {2683-2691}, doi = {10.1002/tox.23628}, pmid = {35920046}, issn = {1522-7278}, mesh = {Acid Phosphatase/metabolism ; Alanine Transaminase/metabolism ; Alkaline Phosphatase/metabolism ; Ammonia ; Animals ; Aspartate Aminotransferases/metabolism ; Bilirubin/metabolism ; *Characiformes ; Complex Mixtures/metabolism/toxicity ; *Cyanobacteria/metabolism ; Glucose/metabolism ; Glycogen/metabolism ; Lactates ; Lipids ; Liver/metabolism ; *Liver Diseases/metabolism ; Microcystins/metabolism/toxicity ; Pyruvates/metabolism ; }, abstract = {Microcystins (MC) are hepatotoxic for organisms. Liver MC accumulation and structural change are intensely studied, but the functional hepatic enzymes and energy metabolism have received little attention. This study investigated the liver and hepatocyte structures and the activity of key hepatic functional enzymes with emphasis on energetic metabolism changes after subchronic fish exposure to cyanobacterial crude extract (CE) containing MC. The Neotropical erythrinid fish, Hoplias malabaricus, were exposed intraperitoneally to CE containing 100 μg MC-LR eq kg[-1] for 30 days and, thereafter, the plasma, liver, and white muscle was sampled for analyses. Liver tissue lost cellular structure organization showing round hepatocytes, hyperemia, and biliary duct obstruction. At the ultrastructural level, the mitochondria and the endoplasmic reticulum exhibited disorganization. Direct and total bilirubin increased in plasma. In the liver, the activity of acid phosphatase (ACP) increased, and the aspartate aminotransferase (AST) decreased; AST increased in plasma. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were unchanged in the liver, muscle, and plasma. Glycogen stores and the energetic metabolites as glucose, lactate, and pyruvate decrease in the liver; pyruvate decreased in plasma and lactate decreased in muscle. Ammonia levels increased and protein concentration decreased in plasma. CE alters liver morphology by causing hepatocyte intracellular disorder, obstructive cholestasis, and dysfunction in the activity of key liver enzymes. The increasing energy demand implies glucose mobilization and metabolic adjustments maintaining protein preservation and lipid recruitment to supply the needs for detoxification allowing fish survival.}, } @article {pmid35915152, year = {2022}, author = {Schavemaker, PE and Muñoz-Gómez, SA}, title = {The role of mitochondrial energetics in the origin and diversification of eukaryotes.}, journal = {Nature ecology & evolution}, volume = {6}, number = {9}, pages = {1307-1317}, pmid = {35915152}, issn = {2397-334X}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; DNA ; *Eukaryota/genetics ; Mitochondria/genetics/metabolism ; Prokaryotic Cells/metabolism ; }, abstract = {The origin of eukaryotic cell size and complexity is often thought to have required an energy excess supplied by mitochondria. Recent observations show energy demands to scale continuously with cell volume, suggesting that eukaryotes do not have higher energetic capacity. However, respiratory membrane area scales superlinearly with the cell surface area. Furthermore, the consequences of the contrasting genomic architectures between prokaryotes and eukaryotes have not been precisely quantified. Here, we investigated (1) the factors that affect the volumes at which prokaryotes become surface area-constrained, (2) the amount of energy divested to DNA due to contrasting genomic architectures and (3) the costs and benefits of respiring symbionts. Our analyses suggest that prokaryotes are not surface area-constrained at volumes of 10[0]‒10[3] µm[3], the genomic architecture of extant eukaryotes is only slightly advantageous at genomes sizes of 10[6]‒10[7] base pairs and a larger host cell may have derived a greater advantage (lower cost) from harbouring ATP-producing symbionts. This suggests that eukaryotes first evolved without the need for mitochondria since these ranges hypothetically encompass the last eukaryotic common ancestor and its relatives. Our analyses also show that larger and faster-dividing prokaryotes would have a shortage of respiratory membrane area and divest more energy into DNA. Thus, we argue that although mitochondria may not have been required by the first eukaryotes, eukaryote diversification was ultimately dependent on mitochondria.}, } @article {pmid35910652, year = {2022}, author = {Yu, J and Ran, Z and Zhang, J and Wei, L and Ma, W}, title = {Genome-Wide Insights Into the Organelle Translocation of Photosynthetic NDH-1 Genes During Evolution.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {956578}, pmid = {35910652}, issn = {1664-302X}, abstract = {Translocation of chloroplast-located genes to mitochondria or nucleus is considered to be a safety strategy that impedes mutation of photosynthetic genes and maintains their household function during evolution. The organelle translocation strategy is also developed in photosynthetic NDH-1 (pNDH-1) genes but its understanding is still far from complete. Here, we found that the mutation rate of the conserved pNDH-1 genes was gradually reduced but their selection pressure was maintained at a high level during evolution from cyanobacteria to angiosperm. By contrast, oxygenic photosynthesis-specific (OPS) pNDH-1 genes had an opposite trend, explaining the reason why they were transferred from the reactive oxygen species (ROS)-enriched chloroplast to the ROS-barren nucleus. Further, genome-wide sequence analysis supported the possibility that all conserved pNDH-1 genes lost in chloroplast genomes of Chlorophyceae and Pinaceae were transferred to the ROS-less mitochondrial genome as deduced from their truncated pNDH-1 gene fragments. Collectively, we propose that the organelle translocation strategy of pNDH-1 genes during evolution is necessary to maintain the function of the pNDH-1 complex as an important antioxidant mechanism for efficient photosynthesis.}, } @article {pmid35899483, year = {2022}, author = {Pani, P and Bal, NC}, title = {Avian adjustments to cold and non-shivering thermogenesis: whats, wheres and hows.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {97}, number = {6}, pages = {2106-2126}, doi = {10.1111/brv.12885}, pmid = {35899483}, issn = {1469-185X}, mesh = {Animals ; *Thermogenesis/physiology ; *Cold Temperature ; Adipose Tissue, Brown/physiology ; Birds ; Muscle, Skeletal/physiology ; Mammals ; Acclimatization/physiology ; }, abstract = {Avian cold adaptation is hallmarked by innovative strategies of both heat conservation and thermogenesis. While minimizing heat loss can reduce the thermogenic demands of body temperature maintenance, it cannot eliminate the requirement for thermogenesis. Shivering and non-shivering thermogenesis (NST) are the two synergistic mechanisms contributing to endothermy. Birds are of particular interest in studies of NST as they lack brown adipose tissue (BAT), the major organ of NST in mammals. Critical analysis of the existing literature on avian strategies of cold adaptation suggests that skeletal muscle is the principal site of NST. Despite recent progress, isolating the mechanisms involved in avian muscle NST has been difficult as shivering and NST co-exist with its primary locomotory function. Herein, we re-evaluate various proposed molecular bases of avian skeletal muscle NST. Experimental evidence suggests that sarco(endo)plasmic reticulum Ca[2+] -ATPase (SERCA) and ryanodine receptor 1 (RyR1) are key in avian muscle NST, through their mediation of futile Ca[2+] cycling and thermogenesis. More recent studies have shown that SERCA regulation by sarcolipin (SLN) facilitates muscle NST in mammals; however, its role in birds is unclear. Ca[2+] signalling in the muscle seems to be common to contraction, shivering and NST, but elucidating its roles will require more precise measurement of local Ca[2+] levels inside avian myofibres. The endocrine control of avian muscle NST is still poorly defined. A better understanding of the mechanistic details of avian muscle NST will provide insights into the roles of these processes in regulatory thermogenesis, which could further inform our understanding of the evolution of endothermy among vertebrates.}, } @article {pmid35895186, year = {2022}, author = {Atayik, MC and Çakatay, U}, title = {Melatonin-related signaling pathways and their regulatory effects in aging organisms.}, journal = {Biogerontology}, volume = {23}, number = {5}, pages = {529-539}, pmid = {35895186}, issn = {1573-6768}, mesh = {Aging/metabolism ; Antioxidants/metabolism ; Free Radicals/metabolism ; Humans ; *Melatonin ; Signal Transduction ; }, abstract = {Melatonin is a tryptophan-derived ancestral molecule evolved in bacteria. According to the endosymbiotic theory, eukaryotic cells received mitochondria, plastids, and other organelles from bacteria by internalization. After the endosymbiosis, bacteria evolved into organelles and retained their ability of producing melatonin. Melatonin is a small, evolutionarily conserved indole with multiple receptor-mediated, receptor-dependent, and independent actions. Melatonin's initial function was likely a radical scavenger in bacteria that's why there was high intensity of free radicals on primitive atmosphere in the ancient times, and hormetic functions of melatonin, which are effecting through the level of gene expression via prooxidant and antioxidant redox pathways, are developed in throughout the eukaryotic evolution. In the earlier stages of life, endosymbiotic events between mitochondria and other downstream organelles continue with mutual benefits. However, this interaction gradually deteriorates as a result of the imperfection of both mitochondrial and extramitochondrial endosymbiotic crosstalk with the advancing age of eukaryotic organisms. Throughout the aging process melatonin levels tend to reduce and as a manifestation of this, many symptoms in organisms' homeostasis, such as deterioration in adjustment of cellular clocks, are commonly seen. In addition, due to deterioration in mitochondrial integrity and functions, immunity decreases, and lower levels of melatonin renders older individuals to be more susceptible to impaired redox modulation and age-related diseases. Our aim in this paper is to focus on the several redox modulation mechanisms in which melatonin signaling has a central role, to discuss melatonin's gerontological aspects and to provide new research ideas with researchers.}, } @article {pmid35893881, year = {2022}, author = {Ghanem, J and Passadori, A and Severac, F and Dieterlen, A and Geny, B and Andrès, E}, title = {Effects of Rehabilitation on Long-COVID-19 Patient's Autonomy, Symptoms and Nutritional Observance.}, journal = {Nutrients}, volume = {14}, number = {15}, pages = {}, pmid = {35893881}, issn = {2072-6643}, mesh = {*COVID-19/complications ; Fatigue/complications ; Humans ; *Malnutrition/diagnosis ; Nutrition Assessment ; Nutritional Status ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Despite significant improvements in COVID-19 therapy, many patients still present with persistent symptoms and quality-of-life alterations. The aim of this study was to simultaneously investigate the long-term evolution of autonomy, malnutrition and long-lasting symptoms in people infected with COVID-19 and hospitalized in the ICU.

METHOD: Patients' clinical characteristics; extent of their loss of autonomy based on "Autonomie Gérontologie Groupes Iso-Ressources" (AG-GIR) classification; nutritional status while following the French and Global Leadership Initiative on Malnutrition (GLIM) recommendations; and symptom evolutions before infection, during hospitalization and rehabilitation, and up to 6 months after returning home were determined in thirty-seven patients.

RESULTS: Prior to a COVID-19 infection, all patients were autonomous, but upon admission to the rehabilitation center (CRM), 39% of them became highly dependent. After discharge from the center and 6 months after returning home, only 6 and 3%, respectively, still required considerable assistance. Of these thirty-seven patients, 11% were moderately malnourished and 81% presented with severe malnutrition, with a significant correlation being observed between malnutrition and autonomy (p < 0.05). Except for fatigue, which persisted in 70% of the patients 6 months after discharge from rehabilitation, all other symptoms decreased significantly.

CONCLUSIONS: This study shows a striking decrease in autonomy associated with malnutrition after hospitalization for a COVID-19 infection and a clear beneficial effect from personalized rehabilitation. However, although almost all patients regained autonomy 6 months after returning home, they often still suffer from fatigue. Patient compliance with their nutritional recommendations deserves further improvement, preferably through personalized and persistent follow-up with the patient.}, } @article {pmid35891364, year = {2022}, author = {Tao, J and Li, B and Cheng, J and Shi, Y and Qiao, C and Lin, Z and Liu, H}, title = {Genomic Divergence Characterization and Quantitative Proteomics Exploration of Type 4 Porcine Astrovirus.}, journal = {Viruses}, volume = {14}, number = {7}, pages = {}, pmid = {35891364}, issn = {1999-4915}, mesh = {Animals ; Antiviral Agents ; *Astroviridae Infections/veterinary ; China ; Genomics ; Humans ; Mamastrovirus ; Mitochondrial Proteins ; Phylogeny ; Proteomics ; Swine ; *Swine Diseases ; }, abstract = {Porcine astrovirus (PAstV) has been identified as an important diarrheic pathogen with a broad global distribution. The PAstV is a potential pathogen to human beings and plays a role in public health. Until now, the divergence characteristics and pathogenesis of the PAstV are still not well known. In this study, the PAstV-4 strain PAstV/CH/2022/CM1 was isolated from the diarrheal feces of a piglet in Shanghai, which was identified to be a recombination of PAstV4/JPN (LC201612) and PAstV4/CHN (JX060808). A time tree based on the ORF2 protein of the astrovirus demonstrated that type 2-5 PAstV (PAstV-2 to 5) diverged from type 1 PAstV (PAstV-1) at a point from 1992 to 2000. To better understand the molecular basis of the virus, we sought to explore the host cell response to the PAstV/CH/2022/CM1 infection using proteomics. The results demonstrate that viral infection elicits global protein changes, and that the mitochondria seems to be a primary and an important target in viral infection. Importantly, there was crosstalk between autophagy and apoptosis, in which ATG7 might be the key mediator. In addition, the NOD-like receptor X1 (NLRX1) in the mitochondria was activated and participated in several important antiviral signaling pathways after the PAstV/CH/2022/CM1 infection, which was closely related to mitophagy. The NLRX1 may be a crucial protein for antagonizing a viral infection through autophagy, but this has yet to be validated. In conclusion, the data in this study provides more information for understanding the virus genomic characterization and the potential antiviral targets in a PAstV infection.}, } @article {pmid35889091, year = {2022}, author = {Mendoza-Hoffmann, F and Zarco-Zavala, M and Ortega, R and Celis-Sandoval, H and Torres-Larios, A and García-Trejo, JJ}, title = {Evolution of the Inhibitory and Non-Inhibitory ε, ζ, and IF1 Subunits of the F1FO-ATPase as Related to the Endosymbiotic Origin of Mitochondria.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, pmid = {35889091}, issn = {2076-2607}, abstract = {The F1FO-ATP synthase nanomotor synthesizes >90% of the cellular ATP of almost all living beings by rotating in the "forward" direction, but it can also consume the same ATP pools by rotating in "reverse." To prevent futile F1FO-ATPase activity, several different inhibitory proteins or domains in bacteria (ε and ζ subunits), mitochondria (IF1), and chloroplasts (ε and γ disulfide) emerged to block the F1FO-ATPase activity selectively. In this study, we analyze how these F1FO-ATPase inhibitory proteins have evolved. The phylogeny of the α-proteobacterial ε showed that it diverged in its C-terminal side, thus losing both the inhibitory function and the ATP-binding/sensor motif that controls this inhibition. The losses of inhibitory function and the ATP-binding site correlate with an evolutionary divergence of non-inhibitory α-proteobacterial ε and mitochondrial δ subunits from inhibitory bacterial and chloroplastidic ε subunits. Here, we confirm the lack of inhibitory function of wild-type and C-terminal truncated ε subunits of P. denitrificans. Taken together, the data show that ζ evolved to replace ε as the primary inhibitor of the F1FO-ATPase of free-living α-proteobacteria. However, the ζ inhibitory function was also partially lost in some symbiotic α-proteobacteria and totally lost in some strictly parasitic α-proteobacteria such as the Rickettsiales order. Finally, we found that ζ and IF1 likely evolved independently via convergent evolution before and after the endosymbiotic origin mitochondria, respectively. This led us to propose the ε and ζ subunits as tracer genes of the pre-endosymbiont that evolved into the actual mitochondria.}, } @article {pmid35883288, year = {2022}, author = {Shang, Y and Wang, X and Liu, G and Wu, X and Wei, Q and Sun, G and Mei, X and Dong, Y and Sha, W and Zhang, H}, title = {Adaptability and Evolution of Gobiidae: A Genetic Exploration.}, journal = {Animals : an open access journal from MDPI}, volume = {12}, number = {14}, pages = {}, pmid = {35883288}, issn = {2076-2615}, abstract = {The Gobiidae family occupy one of the most diverse habitat ranges of all fishes. One key reason for their successful colonization of different habitats is their ability to adapt to different energy demands. This energy requirement is related to the ability of mitochondria in cells to generate energy via oxidative phosphorylation (OXPHOS). Here, we assembled three complete mitochondrial genomes of Rhinogobius shennongensis, Rhinogobius wuyanlingensis, and Chaenogobius annularis. These mitogenomes are circular and include 13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs, and one non-coding control region (CR). We used comparative mitochondrial DNA (mtDNA) genome and selection pressure analyses to explore the structure and evolutionary rates of Gobiidae mitogenomics in different environments. The CmC model showed that the ω ratios of all mtDNA PCGs were <1, and that the evolutionary rate of adenosine triphosphate 8 (atp8) was faster in Gobiidae than in other mitochondrial DNA PCGs. We also found evidence of positive selection for several sites of NADH dehydrogenase (nd) 6 and atp8 genes. Thus, divergent mechanisms appear to underlie the evolution of mtDNA PCGs, which might explain the ability of Gobiidae to adapt to diverse environments. Our study provides new insights on the adaptive evolution of Gobiidae mtDNA genome and molecular mechanisms of OXPHOS.}, } @article {pmid35879672, year = {2022}, author = {Ge, H and Xu, J and Hua, M and An, W and Wu, J and Wang, B and Li, P and Fang, H}, title = {Genome-wide identification and analysis of ACP gene family in Sorghum bicolor (L.) Moench.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {538}, pmid = {35879672}, issn = {1471-2164}, mesh = {Acyl Carrier Protein/genetics/metabolism ; Droughts ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/genetics/metabolism ; *Sorghum/metabolism ; Stress, Physiological/genetics ; Zea mays/genetics/metabolism ; }, abstract = {BACKGROUND: Acyl carrier proteins (ACP) constitute a very conserved carrier protein family. Previous studies have found that ACP not only takes part in the fatty acid synthesis process of almost all organisms, but also participates in the regulation of plant growth, development, and metabolism, and makes plants adaptable to stresses. However, this gene family has not been systematically studied in sorghum.

RESULTS: Nine ACP family members were identified in the sorghum genome, which were located on chromosomes 1, 2, 5, 7, 8 and 9, respectively. Evolutionary analysis among different species divided the ACP family into four subfamilies, showing that the SbACPs were more closely related to maize. The prediction results of subcellular localization showed that SbACPs were mainly distributed in chloroplasts and mitochondria, while fluorescence localization showed that SbACPs were mainly localized in chloroplasts in tobacco leaf. The analysis of gene structure revealed a relatively simple genetic structure, that there were 1-3 introns in the sorghum ACP family, and the gene structure within the same subfamily had high similarity. The amplification method of SbACPs was mainly large fragment replication, and SbACPs were more closely related to ACPs in maize and rice. In addition, three-dimensional structure analysis showed that all ACP genes in sorghum contained four α helices, and the second helix structure was more conserved, implying a key role in function. Cis-acting element analysis indicated that the SbACPs might be involved in light response, plant growth and development regulation, biotic and abiotic stress response, plant hormone regulation, and other physiological processes. What's more, qRT-PCR analysis uncovered that some of SbACPs might be involved in the adaptive regulation of drought and salt stresses, indicating the close relationship between fatty acids and the resistance to abiotic stresses in sorghum.

CONCLUSIONS: In summary, these results showed a comprehensive overview of the SbACPs and provided a theoretical basis for further studies on the biological functions of SbACPs in sorghum growth, development and abiotic stress responses.}, } @article {pmid35877596, year = {2022}, author = {Wu, CS and Chaw, SM}, title = {Evolution of mitochondrial RNA editing in extant gymnosperms.}, journal = {The Plant journal : for cell and molecular biology}, volume = {111}, number = {6}, pages = {1676-1687}, pmid = {35877596}, issn = {1365-313X}, mesh = {Amino Acids ; Cycadopsida/genetics ; *Magnoliopsida/genetics ; Mitochondrial Proteins/genetics ; RNA Editing/genetics ; RNA, Mitochondrial ; *Tracheophyta/genetics ; }, abstract = {To unveil the evolution of mitochondrial RNA editing in gymnosperms, we characterized mitochondrial genomes (mitogenomes), plastid genomes, RNA editing sites, and pentatricopeptide repeat (PPR) proteins from 10 key taxa representing four of the five extant gymnosperm clades. The assembled mitogenomes vary in gene content due to massive gene losses in Gnetum and Conifer II clades. Mitochondrial gene expression levels also vary according to protein function, with the most highly expressed genes involved in the respiratory complex. We identified 9132 mitochondrial C-to-U editing sites, as well as 2846 P-class and 8530 PLS-class PPR proteins. Regains of editing sites were demonstrated in Conifer II rps3 transcripts whose corresponding mitogenomic sequences lack introns due to retroprocessing. Our analyses reveal that non-synonymous editing is efficient and results in more codons encoding hydrophobic amino acids. In contrast, synonymous editing, although performed with variable efficiency, can increase the number of U-ending codons that are preferentially utilized in gymnosperm mitochondria. The inferred loss-to-gain ratio of mitochondrial editing sites in gymnosperms is 2.1:1, of which losses of non-synonymous editing are mainly due to genomic C-to-T substitutions. However, such substitutions only explain a small fraction of synonymous editing site losses, indicating distinct evolutionary mechanisms. We show that gymnosperms have experienced multiple lineage-specific duplications in PLS-class PPR proteins. These duplications likely contribute to accumulated RNA editing sites, as a mechanistic correlation between RNA editing and PLS-class PPR proteins is statistically supported.}, } @article {pmid35875852, year = {2022}, author = {Ebner, JN and Wyss, MK and Ritz, D and von Fumetti, S}, title = {Effects of thermal acclimation on the proteome of the planarian Crenobia alpina from an alpine freshwater spring.}, journal = {The Journal of experimental biology}, volume = {225}, number = {15}, pages = {}, pmid = {35875852}, issn = {1477-9145}, mesh = {Acclimatization/physiology ; Animals ; Climate Change ; Fresh Water ; Humans ; *Planarians ; *Proteome ; Temperature ; }, abstract = {Species' acclimation capacity and their ability to maintain molecular homeostasis outside ideal temperature ranges will partly predict their success following climate change-induced thermal regime shifts. Theory predicts that ectothermic organisms from thermally stable environments have muted plasticity, and that these species may be particularly vulnerable to temperature increases. Whether such species retained or lost acclimation capacity remains largely unknown. We studied proteome changes in the planarian Crenobia alpina, a prominent member of cold-stable alpine habitats that is considered to be a cold-adapted stenotherm. We found that the species' critical thermal maximum (CTmax) is above its experienced habitat temperatures and that different populations exhibit differential CTmax acclimation capacity, whereby an alpine population showed reduced plasticity. In a separate experiment, we acclimated C. alpina individuals from the alpine population to 8, 11, 14 or 17°C over the course of 168 h and compared their comprehensively annotated proteomes. Network analyses of 3399 proteins and protein set enrichment showed that while the species' proteome is overall stable across these temperatures, protein sets functioning in oxidative stress response, mitochondria, protein synthesis and turnover are lower in abundance following warm acclimation. Proteins associated with an unfolded protein response, ciliogenesis, tissue damage repair, development and the innate immune system were higher in abundance following warm acclimation. Our findings suggest that this species has not suffered DNA decay (e.g. loss of heat-shock proteins) during evolution in a cold-stable environment and has retained plasticity in response to elevated temperatures, challenging the notion that stable environments necessarily result in muted plasticity.}, } @article {pmid35870233, year = {2022}, author = {Visinoni, F and Delneri, D}, title = {Mitonuclear interplay in yeast: from speciation to phenotypic adaptation.}, journal = {Current opinion in genetics & development}, volume = {76}, number = {}, pages = {101957}, doi = {10.1016/j.gde.2022.101957}, pmid = {35870233}, issn = {1879-0380}, support = {BB/L021471/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adaptation, Physiological/genetics ; *Hybridization, Genetic ; Mitochondria/genetics/metabolism ; Phenotype ; *Proteome/genetics ; }, abstract = {Saccharomyces yeasts have evolved into an important model system to study mitonuclear incompatibilities, thanks to recent advances in the field of sequencing, yeast hybridisation and multigenerational breeding. Yeast hybrids contain two homologous proteomes but retain only one type of mitochondria allowing studies on the effect of mitochondria on phenotype and gene expression. Here, we discuss the recent developments in the growing field of yeast mitogenomics spanning from the impact that this organelle has in shaping yeast fitness and genome evolution to the dissection of molecular determinants of mitonuclear incompatibilities. Applying the state-of-the-art genetic tools to a broader range of natural yeast species from different environments will help progress the field and untap the mitochondrial potential in strain development.}, } @article {pmid35866365, year = {2022}, author = {McCall, CE and Zhu, X and Zabalawi, M and Long, D and Quinn, MA and Yoza, BK and Stacpoole, PW and Vachharajani, V}, title = {Sepsis, pyruvate, and mitochondria energy supply chain shortage.}, journal = {Journal of leukocyte biology}, volume = {112}, number = {6}, pages = {1509-1514}, doi = {10.1002/JLB.3MR0322-692RR}, pmid = {35866365}, issn = {1938-3673}, mesh = {Mice ; Humans ; Animals ; *Pyruvic Acid/metabolism ; Pyruvate Dehydrogenase Complex/metabolism ; *Sepsis ; Mitochondria/metabolism ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Acetates/pharmacology ; }, abstract = {Balancing high energy-consuming danger resistance and low energy supply of disease tolerance is a universal survival principle that often fails during sepsis. Our research supports the concept that sepsis phosphorylates and deactivates mitochondrial pyruvate dehydrogenase complex control over the tricarboxylic cycle and the electron transport chain. StimulatIng mitochondrial energetics in septic mice and human sepsis cell models can be achieved by inhibiting pyruvate dehydrogenase kinases with the pyruvate structural analog dichloroacetate. Stimulating the pyruvate dehydrogenase complex by dichloroacetate reverses a disruption in the tricarboxylic cycle that induces itaconate, a key mediator of the disease tolerance pathway. Dichloroacetate treatment increases mitochondrial respiration and ATP synthesis, decreases oxidant stress, overcomes metabolic paralysis, regenerates tissue, organ, and innate and adaptive immune cells, and doubles the survival rate in a murine model of sepsis.}, } @article {pmid35862496, year = {2022}, author = {Cadart, C and Heald, R}, title = {Scaling of biosynthesis and metabolism with cell size.}, journal = {Molecular biology of the cell}, volume = {33}, number = {9}, pages = {}, pmid = {35862496}, issn = {1939-4586}, support = {R35 GM118183/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Size ; Humans ; Mitochondria ; *Ploidies ; *Polyploidy ; }, abstract = {Cells adopt a size that is optimal for their function, and pushing them beyond this limit can cause cell aging and death by senescence or reduce proliferative potential. However, by increasing their genome copy number (ploidy), cells can increase their size dramatically and homeostatically maintain physiological properties such as biosynthesis rate. Recent studies investigating the relationship between cell size and rates of biosynthesis and metabolism under normal, polyploid, and pathological conditions are revealing new insights into how cells attain the best function or fitness for their size by tuning processes including transcription, translation, and mitochondrial respiration. A new frontier is to connect single-cell scaling relationships with tissue and whole-organism physiology, which promises to reveal molecular and evolutionary principles underlying the astonishing diversity of size observed across the tree of life.}, } @article {pmid35858057, year = {2022}, author = {Brzęk, P and Roussel, D and Konarzewski, M}, title = {Mice selected for a high basal metabolic rate evolved larger guts but not more efficient mitochondria.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1978}, pages = {20220719}, pmid = {35858057}, issn = {1471-2954}, mesh = {Animals ; *Basal Metabolism ; Mice ; *Mitochondria ; Organ Size ; }, abstract = {Intra-specific variation in both the basal metabolic rate (BMR) and mitochondrial efficiency (the amount of ATP produced per unit of oxygen consumed) has profound evolutionary and ecological consequences. However, the functional mechanisms responsible for this variation are not fully understood. Mitochondrial efficiency is negatively correlated with BMR at the interspecific level but it is positively correlated with performance capacity at the intra-specific level. This discrepancy is surprising, as theories explaining the evolution of endothermy assume a positive correlation between BMR and performance capacity. Here, we quantified mitochondrial oxidative phosphorylation activity and efficiency in two lines of laboratory mice divergently selected for either high (H-BMR) or low (L-BMR) levels of BMR. H-BMR mice had larger livers and kidneys (organs that are important predictors of BMR). H-BMR mice also showed higher oxidative phosphorylation activity in liver mitochondria but this difference can be hypothesized to be a direct effect of selection only if the heritability of this trait is low. However, mitochondrial efficiency in all studied organs did not differ between the two lines. We conclude that the rapid evolution of BMR can reflect changes in organ size rather than mitochondrial properties, and does not need to be accompanied obligatorily by changes in mitochondrial efficiency.}, } @article {pmid35856299, year = {2022}, author = {Carter, CS and Kingsbury, MA}, title = {Oxytocin and oxygen: the evolution of a solution to the 'stress of life'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {377}, number = {1858}, pages = {20210054}, pmid = {35856299}, issn = {1471-2970}, support = {R01 HD098117/HD/NICHD NIH HHS/United States ; R21 HD098603/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Hypothalamo-Hypophyseal System ; Inflammation ; Mammals/metabolism ; Oxygen ; *Oxytocin ; Pituitary-Adrenal System ; Receptors, Oxytocin/metabolism ; }, abstract = {Oxytocin (OT) and the OT receptor occupy essential roles in our current understanding of mammalian evolution, survival, sociality and reproduction. This narrative review examines the hypothesis that many functions attributed to OT can be traced back to conditions on early Earth, including challenges associated with managing life in the presence of oxygen and other basic elements, including sulfur. OT regulates oxidative stress and inflammation especially through effects on the mitochondria. A related nonapeptide, vasopressin, as well as molecules in the hypothalamic-pituitary-adrenal axis, including the corticotropin-releasing hormone family of molecules, have a broad set of functions that interact with OT. Interactions among these molecules have roles in the causes and consequence of social behaviour and the management of threat, fear and stress. Here, we discuss emerging evidence suggesting that unique properties of the OT system allowed vertebrates, and especially mammals, to manage over-reactivity to the 'side effects' of oxygen, including inflammation, oxidation and free radicals, while also supporting high levels of sociality and a perception of safety. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.}, } @article {pmid35850262, year = {2022}, author = {Rottenberg, H}, title = {The accelerated evolution of human cytochrome c oxidase - Selection for reduced rate and proton pumping efficiency?.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1863}, number = {8}, pages = {148595}, doi = {10.1016/j.bbabio.2022.148595}, pmid = {35850262}, issn = {1879-2650}, mesh = {Adenosine Triphosphate ; Animals ; Cattle ; Cytochromes c ; DNA, Mitochondrial ; *Electron Transport Complex IV/genetics/metabolism ; Haplorhini/metabolism ; Humans ; Mammals/metabolism ; Mice ; Oxidoreductases ; Oxygen ; Primates/genetics/metabolism ; *Proton Pumps/genetics ; Protons ; Superoxides ; }, abstract = {The cytochrome c oxidase complex, complex VI (CIV), catalyzes the terminal step of the mitochondrial electron transport chain where the reduction of oxygen to water by cytochrome c is coupled to the generation of a protonmotive force that drive the synthesis of ATP. CIV evolution was greatly accelerated in humans and other anthropoid primates and appears to be driven by adaptive selection. However, it is not known if there are significant functional differences between the anthropoid primates CIV, and other mammals. Comparison of the high-resolution structures of bovine CIV, mouse CIV and human CIV shows structural differences that are associated with anthropoid-specific substitutions. Here I examine the possible effects of these substitutions in four CIV peptides that are known to affect proton pumping: the mtDNA-coded subunits I, II and III, and the nuclear-encoded subunit VIa2. I conclude that many of the anthropoid-specific substitutions could be expected to modulate the rate and/or the efficiency of proton pumping. These results are compatible with the previously proposed hypothesis that the accelerated evolution of CIV in anthropoid primates is driven by selection pressure to lower the mitochondrial protonmotive force and thus decrease the rate of superoxide generation by mitochondria.}, } @article {pmid35842180, year = {2022}, author = {Biró, B and Gál, Z and Schiavo, G and Ribari, A and Joe Utzeri, V and Brookman, M and Fontanesi, L and Hoffmann, OI}, title = {Nuclear mitochondrial DNA sequences in the rabbit genome.}, journal = {Mitochondrion}, volume = {66}, number = {}, pages = {1-6}, doi = {10.1016/j.mito.2022.07.003}, pmid = {35842180}, issn = {1872-8278}, mesh = {Animals ; Cell Nucleus/genetics ; *DNA, Mitochondrial/chemistry/genetics ; Genome ; *Genome, Mitochondrial ; Mammals/genetics ; Mitochondria/genetics ; Phylogeny ; Rabbits ; Sequence Analysis, DNA ; }, abstract = {Numtogenesis is observable in the mammalian genomes resulting in the integration of mitochondrial segments into the nuclear genomes (numts). To identify numts in rabbit, we aligned mitochondrial and nuclear genomes. Alignment significance threshold was calculated and individual characteristics of numts were analysed. We found 153 numts in the nuclear genome. The GC content of numts were significantly lower than the GC content of their genomic flanking regions or the genome itself. The frequency of three mammalian-wide interspersed repeats were increased in the proximity of numts. The decreased GC content around numts strengthen the theory which supposes a link between DNA structural instability and numt integration.}, } @article {pmid35836411, year = {2022}, author = {Shen, LL and Waheed, A and Wang, YP and Nkurikiyimfura, O and Wang, ZH and Yang, LN and Zhan, J}, title = {Mitochondrial Genome Contributes to the Thermal Adaptation of the Oomycete Phytophthora infestans.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {928464}, pmid = {35836411}, issn = {1664-302X}, abstract = {As a vital element of climate change, elevated temperatures resulting from global warming present new challenges to natural and agricultural sustainability, such as ecological disease management. Mitochondria regulate the energy production of cells in responding to environmental fluctuation, but studying their contribution to the thermal adaptation of species is limited. This knowledge is needed to predict future disease epidemiology for ecology conservation and food security. Spatial distributions of the mitochondrial genome (mtDNA) in 405 Phytophthora infestans isolates originating from 15 locations were characterized. The contribution of MtDNA to thermal adaptation was evaluated by comparative analysis of mtDNA frequency and intrinsic growth rate, relative population differentiation in nuclear and mtDNA, and associations of mtDNA distribution with local geography climate conditions. Significant variation in frequency, intrinsic growth rate, and spatial distribution was detected in mtDNA. Population differentiation in mtDNA was significantly higher than that in the nuclear genome, and spatial distribution of mtDNA was strongly associated with local climatic conditions and geographic parameters, particularly air temperature, suggesting natural selection caused by a local temperature is the main driver of the adaptation. Dominant mtDNA grew faster than the less frequent mtDNA. Our results provide useful insights into the evolution of pathogens under global warming. Given its important role in biological functions and adaptation to local air temperature, mtDNA intervention has become an increasing necessity for future disease management. To secure ecological integrity and food production under global warming, a synergistic study on the interactive effect of changing temperature on various components of biological and ecological functions of mitochondria in an evolutionary frame is urgently needed.}, } @article {pmid35809880, year = {2022}, author = {Bononi, G and Masoni, S and Di Bussolo, V and Tuccinardi, T and Granchi, C and Minutolo, F}, title = {Historical perspective of tumor glycolysis: A century with Otto Warburg.}, journal = {Seminars in cancer biology}, volume = {86}, number = {Pt 2}, pages = {325-333}, doi = {10.1016/j.semcancer.2022.07.003}, pmid = {35809880}, issn = {1096-3650}, mesh = {Humans ; *Glycolysis ; *Neoplasms/pathology ; Mitochondria/metabolism ; Oxygen/metabolism ; Lactic Acid/metabolism ; }, abstract = {Tumors have long been known to rewire their metabolism to endorse their proliferation, growth, survival, and invasiveness. One of the common characteristics of these alterations is the enhanced glucose uptake and its subsequent transformation into lactic acid by means of glycolysis, regardless the availability of oxygen or the mitochondria effectiveness. This phenomenon is called the "Warburg effect", which has turned into a century of age now, since its first disclosure by German physiologist Otto Heinrich Warburg. Since then, this peculiar metabolic switch in tumors has been addressed by extensive studies covering several areas of research. In this historical perspective, we aim at illustrating the evolution of these studies over time and their implication in various fields of science.}, } @article {pmid35792646, year = {2022}, author = {Gumińska, N and Milanowski, R}, title = {[Types of circular DNA in Eukarya].}, journal = {Postepy biochemii}, volume = {68}, number = {2}, pages = {129-141}, doi = {10.18388/pb.2021_423}, pmid = {35792646}, issn = {0032-5422}, mesh = {Cell Division ; Cytoplasm ; *DNA, Circular/genetics ; *Eukaryota/genetics ; Mitochondria ; }, abstract = {In eukaryotic cells, DNA occurs mainly in a linear chromosomes. In addition, it can also take the form of circular molecules. Mitochondrial and chloroplast genomes are the most thoroughly studied circular DNAs. However, the repertoire of circular DNA in Eukarya is much broader. It also includes extrachromosomal circular DNA (eccDNA): circular forms of rDNA, telomeric circles, small polydisperse DNA, microDNA, and other types of eccDNA of nuclear origin. The occurrence of eccDNA has been confirmed in all organisms tested so far. Previous studies have shown that some eccDNAs are present at every stage of the cell cycle, while others appear and/or accumulate under specific circumstances. It has been proven that eccDNA accumulation accompanies severe genome destabilization caused by malignancies or stress conditions. Despite growing interest in eccDNA, they remain a poorly understood component of eukaryotic genomes. Still little is known about the mechanisms of their formation, evolution and biological functions.}, } @article {pmid35780856, year = {2022}, author = {Savu, DI and Moisoi, N}, title = {Mitochondria - Nucleus communication in neurodegenerative disease. Who talks first, who talks louder?.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1863}, number = {7}, pages = {148588}, doi = {10.1016/j.bbabio.2022.148588}, pmid = {35780856}, issn = {1879-2650}, mesh = {*Cell Communication ; Cell Nucleus/genetics ; DNA Damage ; Humans ; Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism ; }, abstract = {Mitochondria - nuclear coadaptation has been central to eukaryotic evolution. The dynamic dialogue between the two compartments within the context of multiorganellar interactions is critical for maintaining cellular homeostasis and directing the balance survival-death in case of cellular stress. The conceptualisation of mitochondria - nucleus communication has so far been focused on the communication from the mitochondria under stress to the nucleus and the consequent signalling responses, as well as from the nucleus to mitochondria in the context of DNA damage and repair. During ageing processes this dialogue may be better viewed as an integrated bidirectional 'talk' with feedback loops that expand beyond these two organelles depending on physiological cues. Here we explore the current views on mitochondria - nucleus dialogue and its role in maintaining cellular health with a focus on brain cells and neurodegenerative disease. Thus, we detail the transcriptional responses initiated by mitochondrial dysfunction in order to protect itself and the general cellular homeostasis. Additionally, we are reviewing the knowledge of the stress pathways initiated by DNA damage which affect mitochondria homeostasis and we add the information provided by the study of combined mitochondrial and genotoxic damage. Finally, we reflect on how each organelle may take the lead in this dialogue in an ageing context where both compartments undergo accumulation of stress and damage and where, perhaps, even the communications' mechanisms may suffer interruptions.}, } @article {pmid35776057, year = {2022}, author = {Jardim-Messeder, D and Zamocky, M and Sachetto-Martins, G and Margis-Pinheiro, M}, title = {Chloroplastic ascorbate peroxidases targeted to stroma or thylakoid membrane: The chicken or egg dilemma.}, journal = {FEBS letters}, volume = {596}, number = {23}, pages = {2989-3004}, doi = {10.1002/1873-3468.14438}, pmid = {35776057}, issn = {1873-3468}, mesh = {Ascorbate Peroxidases/genetics/metabolism ; *Thylakoids/metabolism ; Phylogeny ; *Peroxidases/genetics/metabolism ; Chloroplasts/metabolism ; Hydrogen Peroxide/metabolism ; Antioxidants ; Gene Expression Regulation, Plant ; }, abstract = {Ascorbate peroxidases (APXs) are heme peroxidases that remove hydrogen peroxide in different subcellular compartments with concomitant ascorbate cycling. Here, we analysed and discussed phylogenetic and molecular features of the APX family. Ancient APX originated as a soluble stromal enzyme, and early during plant evolution, acquired both chloroplast-targeting and mitochondrion-targeting sequences and an alternative splicing mechanism whereby it could be expressed as a soluble or thylakoid membrane-bound enzyme. Later, independent duplication and neofunctionalization events in some angiosperm groups resulted in individual genes encoding stromal, thylakoidal and mitochondrial isoforms. These data reaffirm the complexity of plant antioxidant defenses that allow diverse plant species to acquire new means to adapt to changing environmental conditions.}, } @article {pmid35766356, year = {2022}, author = {Mondal, S and Kinatukara, P and Singh, S and Shambhavi, S and Patil, GS and Dubey, N and Singh, SH and Pal, B and Shekar, PC and Kamat, SS and Sankaranarayanan, R}, title = {DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35766356}, issn = {2050-084X}, support = {/WT_/Wellcome Trust/United Kingdom ; IA/I/15/2/502058/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, mesh = {Animals ; *Diglycerides/metabolism ; Homeostasis ; Lipid Metabolism ; Mice ; *Saccharomyces cerevisiae/genetics/metabolism ; Triglycerides/metabolism ; }, abstract = {Chain-length-specific subsets of diacylglycerol (DAG) lipids are proposed to regulate differential physiological responses ranging from signal transduction to modulation of the membrane properties. However, the mechanism or molecular players regulating the subsets of DAG species remain unknown. Here, we uncover the role of a conserved eukaryotic protein family, DISCO-interacting protein 2 (DIP2) as a homeostatic regulator of a chemically distinct subset of DAGs using yeast, fly, and mouse models. Genetic and chemical screens along with lipidomics analysis in yeast reveal that DIP2 prevents the toxic accumulation of specific DAGs in the logarithmic growth phase, which otherwise leads to endoplasmic reticulum stress. We also show that the fatty acyl-AMP ligase-like domains of DIP2 are essential for the redirection of the flux of DAG subspecies to storage lipid, triacylglycerols. DIP2 is associated with vacuoles through mitochondria-vacuole contact sites and such modulation of selective DAG abundance by DIP2 is found to be crucial for optimal vacuole membrane fusion and consequently osmoadaptation in yeast. Thus, the study illuminates an unprecedented DAG metabolism route and provides new insights on how cell fine-tunes DAG subspecies for cellular homeostasis and environmental adaptation.}, } @article {pmid35764832, year = {2022}, author = {Kurt, F and Kurt, B and Filiz, E and Yildiz, K and Akbudak, MA}, title = {Mitochondrial iron transporter (MIT) gene in potato (Solanum tuberosum): comparative bioinformatics, physiological and expression analyses in response to drought and salinity.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {35}, number = {5}, pages = {875-887}, pmid = {35764832}, issn = {1572-8773}, mesh = {*Arabidopsis/genetics ; Computational Biology ; Droughts ; Gene Expression Regulation, Plant ; Iron/metabolism ; Membrane Transport Proteins/genetics ; Phylogeny ; Plant Proteins/genetics/metabolism ; Plants/metabolism ; Salinity ; *Solanum tuberosum/genetics/metabolism ; Stress, Physiological/genetics ; }, abstract = {Mitochondrial iron transporter (MIT) genes are essential for mitochondrial acquisition/import of iron and vital to proper functioning of mitochondria. Unlike other organisms, research on the MITs in plants is limited. The present study provides comparative bioinformatics assays for the potato MIT gene (StMIT) as well as gene expression analyses. The phylogenetic analyses revealed monocots-dicot divergence in MIT proteins and it was also found clade specific motif diversity. In addition, docking analyses indicated that Asp172 and Gly100 residues to be identified as the closest residues binding to ferrous iron. The percentage of structure overlap of the StMIT 3D protein model with Arabidopsis, maize and rice MIT proteins was found between 80.18% and 85.71%. The transcript analyses exhibited that the expression of StMIT was triggered under drought and salinity stresses. The findings of the present study would provide valuable leads for further studies targeting specifically the MIT gene and generally the plant iron metabolism.}, } @article {pmid35764697, year = {2022}, author = {Anderson, L and Camus, MF and Monteith, KM and Salminen, TS and Vale, PF}, title = {Variation in mitochondrial DNA affects locomotor activity and sleep in Drosophila melanogaster.}, journal = {Heredity}, volume = {129}, number = {4}, pages = {225-232}, pmid = {35764697}, issn = {1365-2540}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; *DNA, Mitochondrial/genetics ; Drosophila/genetics ; *Drosophila melanogaster/genetics ; Female ; Locomotion/genetics ; Male ; Mitochondria/genetics ; Sleep/genetics ; }, abstract = {Mitochondria are organelles that produce cellular energy in the form of ATP through oxidative phosphorylation, and this primary function is conserved among many taxa. Locomotion is a trait that is highly reliant on metabolic function and expected to be greatly affected by disruptions to mitochondrial performance. To this end, we aimed to examine how activity and sleep vary between Drosophila melanogaster strains with different geographic origins, how these patterns are affected by mitochondrial DNA (mtDNA) variation, and how breaking up co-evolved mito-nuclear gene combinations affect the studied activity traits. Our results demonstrate that Drosophila strains from different locations differ in sleep and activity, and that females are generally more active than males. By comparing activity and sleep of mtDNA variants introgressed onto a common nuclear background in cytoplasmic hybrid (cybrid) strains, we were able to quantify the among-line variance attributable to mitochondrial DNA, and we establish that mtDNA variation affects both activity and sleep, in a sex-specific manner. Altogether our study highlights the important role that mitochondrial genome variation plays on organismal physiology and behaviour.}, } @article {pmid35764672, year = {2022}, author = {Jenkins, HL and Graham, R and Porter, JS and Vieira, LM and de Almeida, ACS and Hall, A and O'Dea, A and Coppard, SE and Waeschenbach, A}, title = {Unprecedented frequency of mitochondrial introns in colonial bilaterians.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {10889}, pmid = {35764672}, issn = {2045-2322}, mesh = {Animals ; *Gene Transfer, Horizontal ; Introns/genetics ; *Mitochondria/genetics ; Phylogeny ; RNA-Directed DNA Polymerase/genetics ; }, abstract = {Animal mitogenomes are typically devoid of introns. Here, we report the largest number of mitochondrial introns ever recorded from bilaterian animals. Mitochondrial introns were identified for the first time from the phylum Bryozoa. They were found in four species from three families (Order Cheilostomatida). A total of eight introns were found in the complete mitogenome of Exechonella vieirai, and five, 17 and 18 introns were found in the partial mitogenomes of Parantropora penelope, Discoporella cookae and Cupuladria biporosa, respectively. Intron-encoded protein domains reverse transcriptase and intron maturase (RVT-IM) were identified in all species. Introns in E. vieirai and P. penelope had conserved Group II intron ribozyme domains V and VI. Conserved domains were lacking from introns in D. cookae and C. biporosa, preventing their further categorization. Putative origins of metazoan introns were explored in a phylogenetic context, using an up-to-date alignment of mitochondrial RVT-IM domains. Results confirmed previous findings of multiple origins of annelid, placozoan and sponge RVT-IM domains and provided evidence for common intron donor sources across metazoan phyla. Our results corroborate growing evidence that some metazoans with regenerative abilities (i.e. placozoans, sponges, annelids and bryozoans) are susceptible to intron integration, most likely via horizontal gene transfer.}, } @article {pmid35758251, year = {2022}, author = {Garrido, C and Wollman, FA and Lafontaine, I}, title = {The Evolutionary History of Peptidases Involved in the Processing of Organelle-Targeting Peptides.}, journal = {Genome biology and evolution}, volume = {14}, number = {7}, pages = {}, pmid = {35758251}, issn = {1759-6653}, mesh = {*Chloroplasts/genetics/metabolism ; Mitochondria/genetics/metabolism ; *Peptide Hydrolases/genetics/metabolism ; Peptides/genetics/metabolism ; Proteolysis ; }, abstract = {Most of the proteins present in mitochondria and chloroplasts, the organelles acquired via endosymbiotic events, are encoded in the nucleus and translated into the cytosol. Most of such nuclear-encoded proteins are specifically recognized via an N-terminal-encoded targeting peptide (TP) and imported into the organelles via a translocon machinery. Once imported, the TP is degraded by a succession of cleavage steps ensured by dedicated peptidases. Here, we retrace the evolution of the families of the mitochondrial processing peptidase (MPP), stromal processing peptidase (SPP), presequence protease (PreP), and organellar oligo-peptidase (OOP) that play a central role in TP processing and degradation across the tree of life. Their bacterial distributions are widespread but patchy, revealing unsurprisingly complex history of lateral transfers among bacteria. We provide evidence for the eukaryotic acquisition of MPP, OOP, and PreP by lateral gene transfers from bacteria at the time of the mitochondrial endosymbiosis. We show that the acquisition of SPP and of a second copy of OOP and PreP at the time of the chloroplast endosymbiosis was followed by a differential loss of one PreP paralog in photosynthetic eukaryotes. We identified some contrasting sequence conservations between bacterial and eukaryotic homologs that could reflect differences in the functional context of their peptidase activity. The close vicinity of the eukaryotic peptidases MPP and OOP to those of several bacterial pathogens, showing antimicrobial resistance, supports a scenario where such bacteria were instrumental in the establishment of the proteolytic pathway for TP degradation in organelles. The evidence for their role in the acquisition of PreP is weaker, and none is observed for SPP, although it cannot be excluded by the present study.}, } @article {pmid35743096, year = {2022}, author = {Ždralević, M and Giannattasio, S}, title = {Mitochondrial Research: Yeast and Human Cells as Models.}, journal = {International journal of molecular sciences}, volume = {23}, number = {12}, pages = {}, pmid = {35743096}, issn = {1422-0067}, mesh = {Humans ; *Mitochondria/metabolism ; Organelles/metabolism ; *Saccharomyces cerevisiae/metabolism ; }, abstract = {The evolution of complex eukaryotes would have been impossible without mitochondria, key cell organelles responsible for the oxidative metabolism of sugars and the bulk of ATP production [...].}, } @article {pmid35741832, year = {2022}, author = {Solana, JC and Chicharro, C and García, E and Aguado, B and Moreno, J and Requena, JM}, title = {Assembly of a Large Collection of Maxicircle Sequences and Their Usefulness for Leishmania Taxonomy and Strain Typing.}, journal = {Genes}, volume = {13}, number = {6}, pages = {}, pmid = {35741832}, issn = {2073-4425}, mesh = {*Genome, Mitochondrial ; Humans ; *Leishmania infantum/genetics ; *Leishmaniasis ; Phylogeny ; *Trypanosoma ; }, abstract = {Parasites of medical importance, such as Leishmania and Trypanosoma, are characterized by the presence of thousands of circular DNA molecules forming a structure known as kinetoplast, within the mitochondria. The maxicircles, which are equivalent to the mitochondrial genome in other eukaryotes, have been proposed as a promising phylogenetic marker. Using whole-DNA sequencing data, it is also possible to assemble maxicircle sequences as shown here and in previous works. In this study, based on data available in public databases and using a bioinformatics workflow previously reported by our group, we assembled the complete coding region of the maxicircles for 26 prototypical strains of trypanosomatid species. Phylogenetic analysis based on this dataset resulted in a robust tree showing an accurate taxonomy of kinetoplastids, which was also able to discern between closely related Leishmania species that are usually difficult to discriminate by classical methodologies. In addition, we provide a dataset of the maxicircle sequences of 60 Leishmania infantum field isolates from America, Western Europe, North Africa, and Eastern Europe. In agreement with previous studies, our data indicate that L. infantum parasites from Brazil are highly homogeneous and closely related to European strains, which were transferred there during the discovery of America. However, this study showed the existence of different L. infantum populations/clades within the Mediterranean region. A maxicircle signature for each clade has been established. Interestingly, two L. infantum clades were found coexisting in the same region of Spain, one similar to the American strains, represented by the Spanish JPCM5 reference strain, and the other, named "non-JPC like", may be related to an important leishmaniasis outbreak that occurred in Madrid a few years ago. In conclusion, the maxicircle sequence emerges as a robust molecular marker for phylogenetic analysis and species typing within the kinetoplastids, which also has the potential to discriminate intraspecific variability.}, } @article {pmid35741788, year = {2022}, author = {Hawkins, MTR and Bailey, CA and Brown, AM and Tinsman, J and Hagenson, RA and Culligan, RR and Barela, AG and Randriamanana, JC and Ranaivoarisoa, JF and Zaonarivelo, JR and Louis, EE}, title = {Nuclear and Mitochondrial Phylogenomics of the Sifakas Reveal Cryptic Variation in the Diademed Sifaka.}, journal = {Genes}, volume = {13}, number = {6}, pages = {}, pmid = {35741788}, issn = {2073-4425}, mesh = {Animals ; Ecosystem ; Humans ; *Indriidae/classification ; Mitochondria ; Phylogeny ; Sea Urchins ; }, abstract = {The most comprehensive phylogenomic reconstruction to date was generated on all nominal taxa within the lemur genus Propithecus. Over 200 wild-caught individuals were included in this study to evaluate the intra and interspecific relationships across this genus. Ultraconserved Elements (UCEs) resulted in well-supported phylogenomic trees. Complete mitochondrial genomes (CMGs) largely agreed with the UCEs, except where a mitochondrial introgression was detected between one clade of the diademed sifaka (Propithecus diadema) and the Milne-Edwards sifaka (P. edwardsi). Additionally, the crowned (P. coronatus) and Von der Decken's (P. deckeni) sifakas belonged to a single admixed lineage from UCEs. Further sampling across these two species is warranted to determine if our sampling represents a hybrid zone. P. diadema recovered two well-supported clades, which were dated and estimated as being ancient as the split between the Perrier's (P. perrierii) and silky (P. candidus) sifakas. The reconstructed demographic history of the two clades also varied over time. We then modeled the modern ecological niches of the two cryptic P. diadema clades and found that they were significantly diverged (p < 0.01). These ecological differences result in a very limited zone of geographic overlap for the P. diadema clades (<60 km[2]). Niche models also revealed that the Onive River acts as a potential barrier to dispersal between P. diadema and P. edwardsi. Further taxonomic work is required on P. diadema to determine if its taxonomic status should be revised. This first genomic evaluation of the genus resolved the relationships between the taxa and the recovered cryptic diversity within one species.}, } @article {pmid35741703, year = {2022}, author = {Orlova, VF and Solovyeva, EN and Dunayev, EA and Ananjeva, NB}, title = {Integrative Taxonomy within Eremias multiocellata Complex (Sauria, Lacertidae) from the Western Part of Range: Evidence from Historical DNA.}, journal = {Genes}, volume = {13}, number = {6}, pages = {}, pmid = {35741703}, issn = {2073-4425}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Lizards/genetics ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The Kokshaal racerunner, Eremias kokshaaliensis Eremchenko et Panfilov, 1999, together with other central Asian racerunner species, is included in the Eremias multiocellata complex. In the present work, for the first time, the results of the analysis of historical mitochondrial DNA (barcode) are presented and the taxonomic status and preliminary phylogenetic relationships within the complex are specified. We present, for the first time, the results of the molecular analysis using historical DNA recovered from specimens of several species of this complex (paratypes of the Kokshaal racerunner and historical collections of the Kashgar racerunner E. buechneri from Kashgaria) using DNA barcoding.}, } @article {pmid35739999, year = {2022}, author = {Martínez-González, JJ and Guevara-Flores, A and Del Arenal Mena, IP}, title = {Evolutionary Adaptations of Parasitic Flatworms to Different Oxygen Tensions.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, pmid = {35739999}, issn = {2076-3921}, abstract = {During the evolution of the Earth, the increase in the atmospheric concentration of oxygen gave rise to the development of organisms with aerobic metabolism, which utilized this molecule as the ultimate electron acceptor, whereas other organisms maintained an anaerobic metabolism. Platyhelminthes exhibit both aerobic and anaerobic metabolism depending on the availability of oxygen in their environment and/or due to differential oxygen tensions during certain stages of their life cycle. As these organisms do not have a circulatory system, gas exchange occurs by the passive diffusion through their body wall. Consequently, the flatworms developed several adaptations related to the oxygen gradient that is established between the aerobic tegument and the cellular parenchyma that is mostly anaerobic. Because of the aerobic metabolism, hydrogen peroxide (H2O2) is produced in abundance. Catalase usually scavenges H2O2 in mammals; however, this enzyme is absent in parasitic platyhelminths. Thus, the architecture of the antioxidant systems is different, depending primarily on the superoxide dismutase, glutathione peroxidase, and peroxiredoxin enzymes represented mainly in the tegument. Here, we discuss the adaptations that parasitic flatworms have developed to be able to transit from the different metabolic conditions to those they are exposed to during their life cycle.}, } @article {pmid35730682, year = {2022}, author = {P, K and Chakraborty, B and Rani, V and Koner, AL}, title = {Rationally designed far-red emitting styryl chromones and a magnetic nanoconjugate for strip-based 'on-site' detection of metabolic markers.}, journal = {Journal of materials chemistry. B}, volume = {10}, number = {26}, pages = {5071-5085}, doi = {10.1039/d2tb00879c}, pmid = {35730682}, issn = {2050-7518}, mesh = {*Chromones ; Fluorescent Dyes/chemistry ; Molecular Docking Simulation ; *Nanoconjugates ; Serum Albumin ; Spectrometry, Fluorescence ; }, abstract = {The global burden of liver damage and renal failure necessitates technology-aided evolution towards point-of-care (POC) testing of metabolic markers. Hence in the prevalence of current health conditions, achieving on-site detection and quantifying serum albumin (SA) can contribute significantly to halting the increased mortality and morbidity rate. Herein, we have rationally designed and synthesized far-red emitting, solvatofluorochromic styryl chromone (SC) derivatives SC1 and SC2, and SC2-conjugated fluorescent magnetic nanoparticles (SCNPs) for sensing SA with a fluorogenic response via interacting at an atypical drug binding site. In solution, the highly sensitive and selective fluorogenic response was evaluated by the prominent amplification and blue-shift in the emission maxima of the probes from deep red to dark yellow through an intermediate orange emission. The transformation of the fluorogen into a fluorophore was manifested through spectroscopic measurements. The stabilization of the probes at protein pockets was ascribed to the non-covalent interactions, such as H-bonding, cation-π, and hydrophobic interactions, as unveiled by docking studies. The practical applications revealed the novelty of SC derivatives through (a) the capability to detect SA isolated from real blood samples via a turn-on fluorescence response; (b) the design of a simple, cheap, and portable test-strip using a glass-slide loaded with solid-state emissive SC2, which provided differential emission color of the SC2-HSA complex in solution and the solid-state with increasing concentration of HSA. Moreover, a smartphone-based color analysis application was employed to obtain the ratio of green and red (G/R) channels, which was utilized for quantitative detection of HSA; (c) the biocompatibility of the SC1 was ascertained through confocal laser scanning microscopic imaging (CLSM). Detailed investigation showed that SC1 could entirely localize in the mitochondria and evolve as a promising biomarker for distinguishing cancer cells from normal cells. Additionally, the validation of uncommon binding of SC1 and SC2 between domains I and III was determined using competition experiments with a known site-specific binder and molecular docking studies. This unique property of the probes can be further exploited to understand the cellular intake of HSA-drug complexes in the multifaceted biological system. These results find the utility of SC derivatives as small molecule-based chemosensors for at-home SA detection and as a biomarker for cancer.}, } @article {pmid35711783, year = {2022}, author = {Della Rocca, G and Papini, A and Posarelli, I and Barberini, S and Tani, C and Danti, R and Moricca, S}, title = {Ultrastructure of Terpene and Polyphenol Synthesis in the Bark of Cupressus sempervirens After Seiridium cardinale Infection.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {886331}, pmid = {35711783}, issn = {1664-302X}, abstract = {Cypress Canker Disease (CCD) pandemic caused by Seiridium cardinale is the major constraint of many Cupressaceae worldwide. One of the main symptoms of the disease is the flow of resin from the cankered barks. While inducible phloem axial resin duct-like structures (PARDs) have recently been characterized from an anatomical point of view, their actual resin production is still being debated and has never been demonstrated. Although the involvement of polyphenolic parenchyma cells (PP cells) in the bark of Cupressus sempervirens after S. cardinale infection was revealed in one of our previous studies using light microscopy, their evolution from the phloem parenchyma cells is yet to be clarified. This study investigated functional and ultrastructural aspects of both PARD-like structures and PP cells by means of more in-depth light (LM) and fluorescence microscopy (FM) combined with histochemical staining (using Sudan red, Fluorol Yellow, NADI Aniline blue black, and Toluidine blue staining), in addition to Transmission Electron Microscope (TEM). Two-year-old stem sections of a C. sempervirens canker-resistant clone (var. "Bolgheri"), artificially inoculated with S. cardinale, were sampled 5, 7, 14, 21, and 45 days after inoculation, for time-course observations. FM observation using Fluorol yellow dye clearly showed the presence of lipid material in PARD-like structures lining cells of the cavity and during their secretion into the duct space/cavity. The same tissues were also positive for NADI staining, revealing the presence of terpenoids. The cytoplasm of the ducts' lining cells was also positive for Sudan red. TEM observation highlighted the involvement of plastids and endoplasmic reticulum in the production of terpenoids and the consequent secretion of terpenoids directly through the plasma membrane, without exhibiting vesicle formation. The presence of a high number of mitochondria around the area of terpenoid production suggests that this process is active and consumes ATP. The LM observations showed that PP cells originated from the phloem parenchyma cells (and possibly albuminous cells) through the accumulation of phenolic substances in the vacuole. Here, plastids were again involved in their production. Thus, the findings of this work suggest that the PARD-like structures can actually be considered PARDs or even bark traumatic resin ducts (BTRD).}, } @article {pmid35706021, year = {2022}, author = {Wu, B and Hao, W and Cox, MP}, title = {Reconstruction of gene innovation associated with major evolutionary transitions in the kingdom Fungi.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {144}, pmid = {35706021}, issn = {1741-7007}, mesh = {Animals ; *Evolution, Molecular ; *Fungi/genetics ; Gene Transfer, Horizontal ; Phylogeny ; Plants/genetics ; }, abstract = {BACKGROUND: Fungi exhibit astonishing diversity with multiple major phenotypic transitions over the kingdom's evolutionary history. As part of this process, fungi developed hyphae, adapted to land environments (terrestrialization), and innovated their sexual structures. These changes also helped fungi establish ecological relationships with other organisms (animals and plants), but the genomic basis of these changes remains largely unknown.

RESULTS: By systematically analyzing 304 genomes from all major fungal groups, together with a broad range of eukaryotic outgroups, we have identified 188 novel orthogroups associated with major changes during the evolution of fungi. Functional annotations suggest that many of these orthogroups were involved in the formation of key trait innovations in extant fungi and are functionally connected. These innovations include components for cell wall formation, functioning of the spindle pole body, polarisome formation, hyphal growth, and mating group signaling. Innovation of mitochondria-localized proteins occurred widely during fungal transitions, indicating their previously unrecognized importance. We also find that prokaryote-derived horizontal gene transfer provided a small source of evolutionary novelty with such genes involved in key metabolic pathways.

CONCLUSIONS: The overall picture is one of a relatively small number of novel genes appearing at major evolutionary transitions in the phylogeny of fungi, with most arising de novo and horizontal gene transfer providing only a small additional source of evolutionary novelty. Our findings contribute to an increasingly detailed portrait of the gene families that define fungal phyla and underpin core features of extant fungi.}, } @article {pmid35701688, year = {2022}, author = {Zheng, J and Zhao, L and Zhao, X and Gao, T and Song, N}, title = {High Genetic Connectivity Inferred from Whole-Genome Resequencing Provides Insight into the Phylogeographic Pattern of Larimichthys polyactis.}, journal = {Marine biotechnology (New York, N.Y.)}, volume = {24}, number = {4}, pages = {671-680}, pmid = {35701688}, issn = {1436-2236}, mesh = {Animals ; Fishes/genetics ; Gene Flow ; Microsatellite Repeats ; *Perciformes/genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Compared with terrestrial biota, marine fishes usually present lower genetic differentiation among different geographical populations because of high-level gene flow and lack of physical barriers. Understanding the genetic structure of marine fishes is essential for dividing management unit and making reasonable protection measures. The small yellow croaker (Larimichthys polyactis) belongs to the family Sciaenidae, which is an economic fish and widely distributed in the Western Pacific. To delineate genetic diversity and phylogeographic pattern, whole-genome resequencing was used to evaluate genetic connectivity, genetic diversity, and spatial pattern of L. polyactis for the first time. We obtained 6,645,711 high-quality single nucleotide polymorphisms (SNPs) markers from 40 L. polyactis individuals. The phylogenetic analysis, STRUCTURE, principal component analysis, and Fst results all indicated that no genetic structure consistent with the distribution pattern was found. This result revealed high genetic connectivity of L. polyactis in different sampling sites. High genetic diversity was also detected, indicating that there was sufficient evolutionary potential to maintain its effective population size. Besides, a similar result of high genetic connectivity and genetic diversity was also detected by mitochondria DNA marker. Our study demonstrated the persistence of high levels of genetic connectivity and a lack of population structure across L. polyactis in different sea areas. This study aimed to analyze the division of population structure and the reason for the decline and not exhaustion of L. polyactis resource on a genetic level.}, } @article {pmid35699132, year = {2022}, author = {Brischigliaro, M and Cabrera-Orefice, A and Sturlese, M and Elurbe, DM and Frigo, E and Fernandez-Vizarra, E and Moro, S and Huynen, MA and Arnold, S and Viscomi, C and Zeviani, M}, title = {CG7630 is the Drosophila melanogaster homolog of the cytochrome c oxidase subunit COX7B.}, journal = {EMBO reports}, volume = {23}, number = {8}, pages = {e54825}, pmid = {35699132}, issn = {1469-3178}, mesh = {Amino Acid Sequence ; Animals ; *Drosophila melanogaster/genetics/metabolism ; *Electron Transport Complex IV/genetics/metabolism ; Mammals/metabolism ; Mitochondria/genetics/metabolism ; Proteomics ; }, abstract = {The mitochondrial respiratory chain (MRC) is composed of four multiheteromeric enzyme complexes. According to the endosymbiotic origin of mitochondria, eukaryotic MRC derives from ancestral proteobacterial respiratory structures consisting of a minimal set of complexes formed by a few subunits associated with redox prosthetic groups. These enzymes, which are the "core" redox centers of respiration, acquired additional subunits, and increased their complexity throughout evolution. Cytochrome c oxidase (COX), the terminal component of MRC, has a highly interspecific heterogeneous composition. Mammalian COX consists of 14 different polypeptides, of which COX7B is considered the evolutionarily youngest subunit. We applied proteomic, biochemical, and genetic approaches to investigate the COX composition in the invertebrate model Drosophila melanogaster. We identified and characterized a novel subunit which is widely different in amino acid sequence, but similar in secondary and tertiary structures to COX7B, and provided evidence that this object is in fact replacing the latter subunit in virtually all protostome invertebrates. These results demonstrate that although individual structures may differ the composition of COX is functionally conserved between vertebrate and invertebrate species.}, } @article {pmid35697683, year = {2022}, author = {Paredes, GF and Viehboeck, T and Markert, S and Mausz, MA and Sato, Y and Liebeke, M and König, L and Bulgheresi, S}, title = {Differential regulation of degradation and immune pathways underlies adaptation of the ectosymbiotic nematode Laxus oneistus to oxic-anoxic interfaces.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {9725}, pmid = {35697683}, issn = {2045-2322}, support = {P28743-B22/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; Chromadorea ; *Chromatiaceae ; Hypoxia ; *Nematoda/microbiology ; Oxygen/metabolism ; Sand ; Sulfides ; Sulfur/metabolism ; }, abstract = {Eukaryotes may experience oxygen deprivation under both physiological and pathological conditions. Because oxygen shortage leads to a reduction in cellular energy production, all eukaryotes studied so far conserve energy by suppressing their metabolism. However, the molecular physiology of animals that naturally and repeatedly experience anoxia is underexplored. One such animal is the marine nematode Laxus oneistus. It thrives, invariably coated by its sulfur-oxidizing symbiont Candidatus Thiosymbion oneisti, in anoxic sulfidic or hypoxic sand. Here, transcriptomics and proteomics showed that, whether in anoxia or not, L. oneistus mostly expressed genes involved in ubiquitination, energy generation, oxidative stress response, immune response, development, and translation. Importantly, ubiquitination genes were also highly expressed when the nematode was subjected to anoxic sulfidic conditions, together with genes involved in autophagy, detoxification and ribosome biogenesis. We hypothesize that these degradation pathways were induced to recycle damaged cellular components (mitochondria) and misfolded proteins into nutrients. Remarkably, when L. oneistus was subjected to anoxic sulfidic conditions, lectin and mucin genes were also upregulated, potentially to promote the attachment of its thiotrophic symbiont. Furthermore, the nematode appeared to survive oxygen deprivation by using an alternative electron carrier (rhodoquinone) and acceptor (fumarate), to rewire the electron transfer chain. On the other hand, under hypoxia, genes involved in costly processes (e.g., amino acid biosynthesis, development, feeding, mating) were upregulated, together with the worm's Toll-like innate immunity pathway and several immune effectors (e.g., bactericidal/permeability-increasing proteins, fungicides). In conclusion, we hypothesize that, in anoxic sulfidic sand, L. oneistus upregulates degradation processes, rewires the oxidative phosphorylation and reinforces its coat of bacterial sulfur-oxidizers. In upper sand layers, instead, it appears to produce broad-range antimicrobials and to exploit oxygen for biosynthesis and development.}, } @article {pmid35695456, year = {2022}, author = {Jiang, X and Coroian, D and Barahona, E and Echavarri-Erasun, C and Castellanos-Rueda, R and Eseverri, Á and Aznar-Moreno, JA and Burén, S and Rubio, LM}, title = {Functional Nitrogenase Cofactor Maturase NifB in Mitochondria and Chloroplasts of Nicotiana benthamiana.}, journal = {mBio}, volume = {13}, number = {3}, pages = {e0026822}, pmid = {35695456}, issn = {2150-7511}, mesh = {*Archaeal Proteins/genetics ; *Azotobacter vinelandii/genetics ; Bacterial Proteins/metabolism ; Chloroplasts/genetics/metabolism ; Fertilizers ; Iron Compounds/*metabolism ; Mitochondria/metabolism ; Nitrogen/metabolism ; Nitrogen Fixation/genetics ; Nitrogenase/genetics/metabolism ; Phylogeny ; Tobacco/genetics/metabolism ; }, abstract = {Engineering plants to synthesize nitrogenase and assimilate atmospheric N2 will reduce crop dependency on industrial N fertilizers. This technology can be achieved by expressing prokaryotic nitrogen fixation gene products for the assembly of a functional nitrogenase in plants. NifB is a critical nitrogenase component since it catalyzes the first committed step in the biosynthesis of all types of nitrogenase active-site cofactors. Here, we used a library of 30 distinct nifB sequences originating from different phyla and ecological niches to restore diazotrophic growth of an Azotobacter vinelandii nifB mutant. Twenty of these variants rescued the nifB mutant phenotype despite their phylogenetic distance to A. vinelandii. Because multiple protein interactions are required in the iron-molybdenum cofactor (FeMo-co) biosynthetic pathway, the maturation of nitrogenase in a heterologous host can be divided in independent modules containing interacting proteins that function together to produce a specific intermediate. Therefore, nifB functional modules composed of a nifB variant, together with the A. vinelandii NifS and NifU proteins (for biosynthesis of NifB [Fe4S4] clusters) and the FdxN ferredoxin (for NifB function), were expressed in Nicotiana benthamiana chloroplasts and mitochondria. Three archaeal NifB proteins accumulated at high levels in soluble fractions of chloroplasts (Methanosarcina acetivorans and Methanocaldococcus infernus) or mitochondria (M. infernus and Methanothermobacter thermautotrophicus). These NifB proteins were shown to accept [Fe4S4] clusters from NifU and were functional in FeMo-co synthesis in vitro. The accumulation of significant levels of soluble and functional NifB proteins in chloroplasts and mitochondria is critical to engineering biological nitrogen fixation in plants. IMPORTANCE Biological nitrogen fixation is the conversion of inert atmospheric dinitrogen gas into nitrogen-reactive ammonia, a reaction catalyzed by the nitrogenase enzyme of diazotrophic bacteria and archaea. Because plants cannot fix their own nitrogen, introducing functional nitrogenase in cereals and other crop plants would reduce our strong dependency on N fertilizers. NifB is required for the biosynthesis of the active site cofactors of all nitrogenases, which arguably makes it the most important protein in global nitrogen fixation. NifB functionality is therefore a requisite to engineer a plant nitrogenase. The expression of nifB genes from a wide range of prokaryotes into the model diazotroph Azotobacter vinelandii shows a surprising level of genetic complementation suggestive of plasticity in the nitrogenase biosynthetic pathway. In addition, we obtained NifB proteins from both mitochondria and chloroplasts of tobacco that are functional in vitro after reconstitution by providing [Fe4S4] clusters from NifU, paving the way to nitrogenase cofactor biosynthesis in plants.}, } @article {pmid35688936, year = {2022}, author = {Groux, K and Verschueren, A and Nanteau, C and Clémençon, M and Fink, M and Sahel, JA and Boccara, C and Paques, M and Reichman, S and Grieve, K}, title = {Dynamic full-field optical coherence tomography allows live imaging of retinal pigment epithelium stress model.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {575}, pmid = {35688936}, issn = {2399-3642}, mesh = {Animals ; Fluorescein Angiography ; Humans ; *Macular Degeneration/metabolism ; Mitochondria ; *Retinal Pigment Epithelium/metabolism ; Swine ; Tomography, Optical Coherence/methods ; }, abstract = {Retinal degenerative diseases lead to the blindness of millions of people around the world. In case of age-related macular degeneration (AMD), the atrophy of retinal pigment epithelium (RPE) precedes neural dystrophy. But as crucial as understanding both healthy and pathological RPE cell physiology is for those diseases, no current technique allows subcellular in vivo or in vitro live observation of this critical cell layer. To fill this gap, we propose dynamic full-field OCT (D-FFOCT) as a candidate for live observation of in vitro RPE phenotype. In this way, we monitored primary porcine and human stem cell-derived RPE cells in stress model conditions by performing scratch assays. In this study, we quantified wound healing parameters on the stressed RPE, and observed different cell phenotypes, displayed by the D-FFOCT signal. In order to decipher the subcellular contributions to these dynamic profiles, we performed immunohistochemistry to identify which organelles generate the signal and found mitochondria to be the main contributor to D-FFOCT contrast. Altogether, D-FFOCT appears to be an innovative method to follow degenerative disease evolution and could be an appreciated method in the future for live patient diagnostics and to direct treatment choice.}, } @article {pmid35683389, year = {2022}, author = {Ruiz, D and Santibañez, M and Lavín, BA and Berja, A and Montalban, C and Vazquez, LA}, title = {Evolution of Mitochondrially Derived Peptides Humanin and MOTSc, and Changes in Insulin Sensitivity during Early Gestation in Women with and without Gestational Diabetes.}, journal = {Journal of clinical medicine}, volume = {11}, number = {11}, pages = {}, pmid = {35683389}, issn = {2077-0383}, abstract = {Our purpose is to study the evolution of mitochondrially derived peptides (MDPs) and their relationship with changes in insulin sensitivity from the early stages of pregnancy in a cohort of pregnant women with and without gestational diabetes (GDM). MDPs (humanin and MOTSc) were assessed in the first and second trimesters of gestation in 28 pregnant women with gestational diabetes mellitus (GDM) and a subgroup of 45 pregnant women without GDM matched by BMI, age, previous gestations, and time of sampling. Insulin resistance (IR) was defined as a HOMA-IR index ≥70th percentile. We observed a significant reduction in both humanin and MOTSc levels from the first to the second trimesters of pregnancy. After adjusting for predefined variables, including BMI, statistically nonsignificant associations between lower levels of humanin and the occurrence of a high HOMA-IR index were obtained (adjusted OR = 2.63 and 3.14 for the first and second trimesters, linear p-trend 0.260 and 0.175, respectively). Regarding MOTSc, an association was found only for the second trimester: adjusted OR = 7.68 (95% CI 1.49-39.67), linear p-trend = 0.012. No significant associations were observed in humanin change with insulin resistance throughout pregnancy, but changes in MOTSc levels were significantly associated with HOMA-IR index: adjusted OR 3.73 (95% CI 1.03-13.50). In conclusion, MOTSc levels, especially a strong decrease from the first to second trimester of gestation, may be involved in increasing insulin resistance during early gestation.}, } @article {pmid35682820, year = {2022}, author = {Cartalas, J and Coudray, L and Gobert, A}, title = {How RNases Shape Mitochondrial Transcriptomes.}, journal = {International journal of molecular sciences}, volume = {23}, number = {11}, pages = {}, pmid = {35682820}, issn = {1422-0067}, mesh = {Endoribonucleases/metabolism ; Eukaryota/genetics/metabolism ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/metabolism ; RNA/metabolism ; *Ribonucleases/metabolism ; *Transcriptome ; }, abstract = {Mitochondria are the power houses of eukaryote cells. These endosymbiotic organelles of prokaryote origin are considered as semi-autonomous since they have retained a genome and fully functional gene expression mechanisms. These pathways are particularly interesting because they combine features inherited from the bacterial ancestor of mitochondria with characteristics that appeared during eukaryote evolution. RNA biology is thus particularly diverse in mitochondria. It involves an unexpectedly vast array of factors, some of which being universal to all mitochondria and others being specific from specific eukaryote clades. Among them, ribonucleases are particularly prominent. They play pivotal functions such as the maturation of transcript ends, RNA degradation and surveillance functions that are required to attain the pool of mature RNAs required to synthesize essential mitochondrial proteins such as respiratory chain proteins. Beyond these functions, mitochondrial ribonucleases are also involved in the maintenance and replication of mitochondrial DNA, and even possibly in the biogenesis of mitochondrial ribosomes. The diversity of mitochondrial RNases is reviewed here, showing for instance how in some cases a bacterial-type enzyme was kept in some eukaryotes, while in other clades, eukaryote specific enzymes were recruited for the same function.}, } @article {pmid35682809, year = {2022}, author = {Eugenin, E and Camporesi, E and Peracchia, C}, title = {Direct Cell-Cell Communication via Membrane Pores, Gap Junction Channels, and Tunneling Nanotubes: Medical Relevance of Mitochondrial Exchange.}, journal = {International journal of molecular sciences}, volume = {23}, number = {11}, pages = {}, pmid = {35682809}, issn = {1422-0067}, mesh = {Animals ; Cell Communication/physiology ; Cell Membrane Structures ; *Gap Junctions/metabolism ; Ion Channels/metabolism ; Mitochondria ; *Nanotubes/chemistry ; }, abstract = {The history of direct cell-cell communication has evolved in several small steps. First discovered in the 1930s in invertebrate nervous systems, it was thought at first to be an exception to the "cell theory", restricted to invertebrates. Surprisingly, however, in the 1950s, electrical cell-cell communication was also reported in vertebrates. Once more, it was thought to be an exception restricted to excitable cells. In contrast, in the mid-1960s, two startling publications proved that virtually all cells freely exchange small neutral and charged molecules. Soon after, cell-cell communication by gap junction channels was reported. While gap junctions are the major means of cell-cell communication, in the early 1980s, evidence surfaced that some cells might also communicate via membrane pores. Questions were raised about the possible artifactual nature of the pores. However, early in this century, we learned that communication via membrane pores exists and plays a major role in medicine, as the structures involved, "tunneling nanotubes", can rescue diseased cells by directly transferring healthy mitochondria into compromised cells and tissues. On the other hand, pathogens/cancer could also use these communication systems to amplify pathogenesis. Here, we describe the evolution of the discovery of these new communication systems and the potential therapeutic impact on several uncurable diseases.}, } @article {pmid35673874, year = {2022}, author = {Tassé, M and Choquette, T and Angers, A and Stewart, DT and Pante, E and Breton, S}, title = {The longest mitochondrial protein in metazoans is encoded by the male-transmitted mitogenome of the bivalve Scrobicularia plana.}, journal = {Biology letters}, volume = {18}, number = {6}, pages = {20220122}, pmid = {35673874}, issn = {1744-957X}, mesh = {Amino Acids/genetics/metabolism ; Animals ; *Bivalvia/genetics/metabolism ; Cyclooxygenase 2/genetics/metabolism ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; Male ; Mitochondrial Proteins/genetics ; }, abstract = {Cytochrome c oxidase subunit II (COX2) is one of the three mitochondrially encoded proteins of the complex IV of the respiratory chain that catalyses the reduction of oxygen to water. The cox2 gene spans about 690 base pairs in most animal species and produces a protein composed of approximately 230 amino acids. We discovered an extreme departure from this pattern in the male-transmitted mitogenome of the bivalve Scrobicularia plana with doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA), which possesses an important in-frame insertion of approximately 4.8 kb in its cox2 gene. This feature-an enlarged male cox2 gene-is found in many species with DUI; the COX2 protein can be up to 420 amino acids long. Through RT-PCRs, immunoassays and comparative genetics, the evolution and functionality of this insertion in S. plana were characterized. The in-frame insertion is conserved among individuals from different populations and bears the signature of purifying selection seemingly indicating maintenance of functionality. Its transcription and translation were confirmed: this gene produces a polypeptide of 1892 amino acids, making it the largest metazoan COX2 protein known to date. We hypothesize that these extreme modifications in the COX2 protein affect the metabolism of mitochondria containing the male-transmitted mtDNA in Scrobicularia plana.}, } @article {pmid35670055, year = {2022}, author = {Choudhury, S and Ananthanarayanan, V and Ayappa, KG}, title = {Coupling of mitochondrial population evolution to microtubule dynamics in fission yeast cells: a kinetic Monte Carlo study.}, journal = {Soft matter}, volume = {18}, number = {23}, pages = {4483-4492}, doi = {10.1039/d2sm00155a}, pmid = {35670055}, issn = {1744-6848}, mesh = {Kinetics ; Microtubules/metabolism ; Mitochondria ; Monte Carlo Method ; *Schizosaccharomyces/genetics ; }, abstract = {Mitochondrial populations in cells are maintained by cycles of fission and fusion events. Perturbation of this balance has been observed in several diseases such as cancer and neurodegeneration. In fission yeast cells, the association of mitochondria with microtubules inhibits mitochondrial fission [Mehta et al., J. Biol. Chem., 2019, 294, 3385], illustrating the intricate coupling between mitochondria and the dynamic population of microtubules within the cell. In order to understand this coupling, we carried out kinetic Monte Carlo (KMC) simulations to predict the evolution of mitochondrial size distributions for different cases; wild-type cells, cells with short and long microtubules, and cells without microtubules. Comparisons are made with mitochondrial distributions reported in experiments with fission yeast cells. Using experimentally determined mitochondrial fission and fusion frequencies, simulations implemented without the coupling of microtubule dynamics predicted an increase in the mean number of mitochondria, equilibrating within 50 s. The mitochondrial length distribution in these models also showed a higher occurrence of shorter mitochondria, implying a greater tendency for fission, similar to the scenario observed in the absence of microtubules and cells with short microtubules. Interestingly, this resulted in overestimating the mean number of mitochondria and underestimating mitochondrial lengths in cells with wild-type and long microtubules. However, coupling mitochondria's fission and fusion events to the microtubule dynamics effectively captured the mitochondrial number and size distributions in wild-type and cells with long microtubules. Thus, the model provides greater physical insight into the temporal evolution of mitochondrial populations in different microtubule environments, allowing one to study both the short-time evolution as observed in the experiments (<5 minutes) as well as their transition towards a steady-state (>15 minutes). Our study illustrates the critical role of microtubules in mitochondrial dynamics and coupling microtubule growth and shrinkage dynamics is critical to predicting the evolution of mitochondrial populations within the cell.}, } @article {pmid35666201, year = {2022}, author = {Simon, M and Durand, S and Ricou, A and Vrielynck, N and Mayjonade, B and Gouzy, J and Boyer, R and Roux, F and Camilleri, C and Budar, F}, title = {APOK3, a pollen killer antidote in Arabidopsis thaliana.}, journal = {Genetics}, volume = {221}, number = {4}, pages = {}, pmid = {35666201}, issn = {1943-2631}, mesh = {Alleles ; Antidotes/metabolism ; *Arabidopsis/genetics/metabolism ; *Poisons/metabolism ; Pollen/genetics ; }, abstract = {The principles of heredity state that the two alleles carried by a heterozygote are equally transmitted to the progeny. However, genomic regions that escape this rule have been reported in many organisms. It is notably the case of genetic loci referred to as gamete killers, where one allele enhances its transmission by causing the death of the gametes that do not carry it. Gamete killers are of great interest, particularly to understand mechanisms of evolution and speciation. Although being common in plants, only a few, all in rice, have so far been deciphered to the causal genes. Here, we studied a pollen killer found in hybrids between two accessions of Arabidopsis thaliana. Exploring natural variation, we observed this pollen killer in many crosses within the species. Genetic analyses revealed that three genetically linked elements are necessary for pollen killer activity. Using mutants, we showed that this pollen killer works according to a poison-antidote model, where the poison kills pollen grains not producing the antidote. We identified the gene encoding the antidote, a chimeric protein addressed to mitochondria. De novo genomic sequencing in 12 natural variants with different behaviors regarding the pollen killer revealed a hyper variable locus, with important structural variations particularly in killer genotypes, where the antidote gene recently underwent duplications. Our results strongly suggest that the gene has newly evolved within A. thaliana. Finally, we identified in the protein sequence polymorphisms related to its antidote activity.}, } @article {pmid35661419, year = {2022}, author = {Dawson, NJ and Scott, GR}, title = {Adaptive increases in respiratory capacity and O2 affinity of subsarcolemmal mitochondria from skeletal muscle of high-altitude deer mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {36}, number = {7}, pages = {e22391}, doi = {10.1096/fj.202200219R}, pmid = {35661419}, issn = {1530-6860}, mesh = {*Altitude ; Animals ; Hypoxia ; Mitochondria ; Mitochondria, Muscle ; Muscle, Skeletal ; *Peromyscus/physiology ; }, abstract = {Aerobic energy demands have led to the evolution of complex mitochondrial reticula in highly oxidative muscles, but the extent to which metabolic challenges can be met with adaptive changes in physiology of specific mitochondrial fractions remains unresolved. We examined mitochondrial mechanisms supporting adaptive increases in aerobic performance in deer mice (Peromyscus maniculatus) adapted to the hypoxic environment at high altitude. High-altitude and low-altitude mice were born and raised in captivity, and exposed as adults to normoxia or hypobaric hypoxia (12 kPa O2 for 6-8 weeks). Subsarcolemmal and intermyofibrillar mitochondria were isolated from the gastrocnemius, and a comprehensive substrate titration protocol was used to examine mitochondrial physiology and O2 kinetics by high-resolution respirometry and fluorometry. High-altitude mice had greater yield, respiratory capacity for oxidative phosphorylation, and O2 affinity (lower P50) of subsarcolemmal mitochondria compared to low-altitude mice across environments, but there were no species difference in these traits in intermyofibrillar mitochondria. High-altitude mice also had greater capacities of complex II relative to complexes I + II and higher succinate dehydrogenase activities in both mitochondrial fractions. Exposure to chronic hypoxia reduced reactive oxygen species (ROS) emission in high-altitude mice but not in low-altitude mice. Our findings suggest that functional changes in subsarcolemmal mitochondria contribute to improving aerobic performance in hypoxia in high-altitude deer mice. Therefore, physiological variation in specific mitochondrial fractions can help overcome the metabolic challenges of life at high altitude.}, } @article {pmid35654156, year = {2022}, author = {Hautekiet, P and Saenen, ND and Aerts, R and Martens, DS and Roels, HA and Bijnens, EM and Nawrot, TS}, title = {Higher buccal mtDNA content is associated with residential surrounding green in a panel study of primary school children.}, journal = {Environmental research}, volume = {213}, number = {}, pages = {113551}, doi = {10.1016/j.envres.2022.113551}, pmid = {35654156}, issn = {1096-0953}, mesh = {Child ; *DNA, Mitochondrial/genetics ; Ethnicity ; Humans ; Mitochondria ; *Parks, Recreational ; Residence Characteristics ; Schools ; }, abstract = {BACKGROUND: Mitochondria are known to respond to environmental stressors but whether green space is associated with mitochondrial abundance is unexplored. Furthermore, as exposures may affect health from early life onwards, we here evaluate if residential green space is associated with mitochondria DNA content (mtDNAc) in children.

METHODS: In primary schoolchildren (COGNAC study), between 2012 and 2014, buccal mtDNAc was repeatedly (three times) assessed using qPCR. Surrounding low (<3m), high (≥3m) and total (sum of low and high) green space within different radii (100m-1000m) from the residence and distance to the nearest large green space (>0.5ha) were estimated using a remote sensing derived map. Given the repeated measures design, we applied a mixed-effects model with school and subject as random effect while adjusting for a priori chosen fixed covariates.

RESULTS: mtDNAc was assessed in 246 children with a total of 436 measurements (mean age 10.3 years). Within a 1000m radius around the residential address, an IQR increment in low (11.0%), high (9.5%), and total (13.9%) green space was associated with a respectively 15.2% (95% CI: 7.2%-23.7%), 10.8% (95% CI: 4.5%-17.5%), and 13.4% (95% CI: 7.4%-19.7%) higher mtDNAc. Conversely, an IQR increment (11.6%) in agricultural area in the same radius was associated with a -3.4% (95% CI: 6.7% to -0.1%) lower mtDNAc. Finally, a doubling in distance to large green space was associated with a -5.2% (95% CI: 7.9 to -2.4%) lower mtDNAc.

CONCLUSION: To our knowledge, this is the first study evaluating associations between residential surrounding green space and mtDNAc in children. Our results showed that green space was associated with a higher mtDNAc in children, which indicates the importance of the early life environment. To what extent these findings contribute to later life health effects should be further examined.}, } @article {pmid35642316, year = {2022}, author = {Bremer, N and Tria, FDK and Skejo, J and Garg, SG and Martin, WF}, title = {Ancestral State Reconstructions Trace Mitochondria But Not Phagocytosis to the Last Eukaryotic Common Ancestor.}, journal = {Genome biology and evolution}, volume = {14}, number = {6}, pages = {}, pmid = {35642316}, issn = {1759-6653}, mesh = {Animals ; *Biological Evolution ; *Eukaryota/genetics ; Eukaryotic Cells/physiology ; Mitochondria/genetics ; Phagocytosis/physiology ; Phylogeny ; Symbiosis/genetics ; }, abstract = {Two main theories have been put forward to explain the origin of mitochondria in eukaryotes: phagotrophic engulfment (undigested food) and microbial symbiosis (physiological interactions). The two theories generate mutually exclusive predictions about the order in which mitochondria and phagocytosis arose. To discriminate the alternatives, we have employed ancestral state reconstructions (ASR) for phagocytosis as a trait, phagotrophy as a feeding habit, the presence of mitochondria, the presence of plastids, and the multinucleated organization across major eukaryotic lineages. To mitigate the bias introduced by assuming a particular eukaryotic phylogeny, we reconstructed the appearance of these traits across 1789 different rooted gene trees, each having species from opisthokonts, mycetozoa, hacrobia, excavate, archeplastida, and Stramenopiles, Alveolates and Rhizaria. The trees reflect conflicting relationships and different positions of the root. We employed a novel phylogenomic test that summarizes ASR across trees which reconstructs a last eukaryotic common ancestor that possessed mitochondria, was multinucleated, lacked plastids, and was non-phagotrophic as well as non-phagocytic. This indicates that both phagocytosis and phagotrophy arose subsequent to the origin of mitochondria, consistent with findings from comparative physiology. Furthermore, our ASRs uncovered multiple origins of phagocytosis and of phagotrophy across eukaryotes, indicating that, like wings in animals, these traits are useful but neither ancestral nor homologous across groups. The data indicate that mitochondria preceded the origin of phagocytosis, such that phagocytosis cannot have been the mechanism by which mitochondria were acquired.}, } @article {pmid35639693, year = {2022}, author = {Calatrava, V and Stephens, TG and Gabr, A and Bhaya, D and Bhattacharya, D and Grossman, AR}, title = {Retrotransposition facilitated the establishment of a primary plastid in the thecate amoeba Paulinella.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {23}, pages = {e2121241119}, pmid = {35639693}, issn = {1091-6490}, mesh = {*Amoeba/genetics ; *Biological Evolution ; Eukaryota/genetics ; Plastids/genetics ; *Rhizaria ; *Symbiosis/genetics ; }, abstract = {The evolution of eukaryotic life was predicated on the development of organelles such as mitochondria and plastids. During this complex process of organellogenesis, the host cell and the engulfed prokaryote became genetically codependent, with the integration of genes from the endosymbiont into the host nuclear genome and subsequent gene loss from the endosymbiont. This process required that horizontally transferred genes become active and properly regulated despite inherent differences in genetic features between donor (endosymbiont) and recipient (host). Although this genetic reorganization is considered critical for early stages of organellogenesis, we have little knowledge about the mechanisms governing this process. The photosynthetic amoeba Paulinella micropora offers a unique opportunity to study early evolutionary events associated with organellogenesis and primary endosymbiosis. This amoeba harbors a “chromatophore,” a nascent photosynthetic organelle derived from a relatively recent cyanobacterial association (∼120 million years ago) that is independent of the evolution of primary plastids in plants (initiated ∼1.5 billion years ago). Analysis of the genome and transcriptome of Paulinella revealed that retrotransposition of endosymbiont-derived nuclear genes was critical for their domestication in the host. These retrocopied genes involved in photoprotection in cyanobacteria became expanded gene families and were “rewired,” acquiring light-responsive regulatory elements that function in the host. The establishment of host control of endosymbiont-derived genes likely enabled the cell to withstand photo-oxidative stress generated by oxygenic photosynthesis in the nascent organelle. These results provide insights into the genetic mechanisms and evolutionary pressures that facilitated the metabolic integration of the host–endosymbiont association and sustained the evolution of a photosynthetic organelle.}, } @article {pmid35638362, year = {2022}, author = {Li, M and Chen, WT and Zhang, QL and Liu, M and Xing, CW and Cao, Y and Luo, FZ and Yuan, ML}, title = {Mitochondrial phylogenomics provides insights into the phylogeny and evolution of spiders (Arthropoda: Araneae).}, journal = {Zoological research}, volume = {43}, number = {4}, pages = {566-584}, pmid = {35638362}, issn = {2095-8137}, mesh = {Animals ; *Arthropods ; *Genome, Mitochondrial/genetics ; Mitochondria/genetics ; Phylogeny ; RNA, Transfer/genetics ; *Spiders/genetics ; }, abstract = {Spiders are among the most varied terrestrial predators, with highly diverse morphology, ecology, and behavior. Morphological and molecular data have greatly contributed to advances in the phylogeny and evolutionary dynamics of spiders. Here, we performed comprehensive mitochondrial phylogenomics analysis on 78 mitochondrial genomes (mitogenomes) representing 29 families; of these, 23 species from eight families were newly generated. Mesothelae retained the same gene arrangement as the arthropod ancestor (Limulus polyphemus), while Opisthothelae showed extensive rearrangement, with 12 rearrangement types in transfer RNAs (tRNAs) and control region. Most spider tRNAs were extremely truncated and lacked typical dihydrouridine or TΨC arms, showing high tRNA structural diversity; in particular, trnS1 exhibited anticodon diversity across the phylogeny. The evolutionary rates of mitochondrial genes were potentially associated with gene rearrangement or truncated tRNAs. Both mitogenomic sequences and rearrangements possessed phylogenetic characteristics, providing a robust backbone for spider phylogeny, as previously reported. The monophyly of suborder, infraorder, retrolateral tibial apophysis clade, and families (except for Pisauridae) was separately supported, and high-level relationships were resolved as (Mesothelae, (Mygalomorphae, (Entelegynae, (Synspermiata, Hypochilidae)))). The phylogenetic positions of several families were also resolved (e.g., Eresidae, Oecobiidae and Titanoecidae). Two reconstructions of ancestral web type obtained almost identical results, indicating that the common ancestor of spiders likely foraged using a silk-lined burrow. This study, the largest mitochondrial phylogenomics analysis of spiders to date, highlights the usefulness of mitogenomic data not only for providing efficient phylogenetic signals for spider phylogeny, but also for characterizing trait diversification in spider evolution.}, } @article {pmid35637201, year = {2022}, author = {Kodama, Y and Fujishima, M}, title = {Endosymbiotic Chlorella variabilis reduces mitochondrial number in the ciliate Paramecium bursaria.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {8216}, pmid = {35637201}, issn = {2045-2322}, mesh = {Antibodies, Monoclonal/metabolism ; *Chlorella/metabolism ; Mitochondria ; *Paramecium/metabolism ; Symbiosis ; }, abstract = {Extant symbioses illustrate endosymbiosis is a driving force for evolution and diversification. In the ciliate Paramecium bursaria, the endosymbiotic alga Chlorella variabilis in perialgal vacuole localizes beneath the host cell cortex by adhesion between the perialgal vacuole membrane and host mitochondria. We investigated whether host mitochondria are also affected by algal endosymbiosis. Transmission electron microscopy of host cells showed fewer mitochondria beneath the algae-bearing host cell cortex than that of alga-free cells. To compare the density and distribution of host mitochondria with or without symbiotic algae, we developed a monoclonal antibody against Paramecium mitochondria. Immunofluorescence microscopy with the monoclonal antibody showed that the mitochondrial density of the algae-bearing P. bursaria was significantly lower than that of the alga-free cells. The total cell protein concentration of alga-free P. bursaria cells was approximately 1.8-fold higher than that of algae-bearing cells, and the protein content of mitochondria was significantly higher in alga-free cells than that in the algae-bearing cells. These results corresponded with those obtained by transmission electron and immunofluorescence microscopies. This paper shows that endosymbiotic algae affect reduced mitochondrial number in the host P. bursaria significantly.}, } @article {pmid35636077, year = {2022}, author = {Jiang, YJ and Jin, J and Nan, QY and Ding, J and Cui, S and Xuan, MY and Piao, MH and Piao, SG and Zheng, HL and Jin, JZ and Chung, BH and Yang, CW and Li, C}, title = {Coenzyme Q10 attenuates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in unilateral ureteral obstruction.}, journal = {International immunopharmacology}, volume = {108}, number = {}, pages = {108868}, doi = {10.1016/j.intimp.2022.108868}, pmid = {35636077}, issn = {1878-1705}, mesh = {Animals ; Fibrosis ; Glycogen Synthase Kinase 3 beta ; Hydrogen Peroxide/pharmacology ; Intracellular Signaling Peptides and Proteins/metabolism ; Kidney/pathology ; *Kidney Diseases/drug therapy/pathology ; Protein Kinases/metabolism ; Rats ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Ubiquinone/analogs & derivatives ; *Ureteral Obstruction/drug therapy ; beta Catenin ; }, abstract = {OBJECTIVE: Coenzyme Q10 (CoQ10) protects against various types of injury, but its role in preventing renal scarring in chronic kidney disease remains an open question. Herein, we evaluated whether CoQ10 attenuates renal fibrosis by interfering with necroinflammation in a rat model of unilateral ureteral obstruction (UUO) and in vitro.

METHODS: Rats with UUO were treated daily with CoQ10 or an RIP inhibitor (necrostatin-1 or GSK872) for 7 days. The influence of CoQ10 on renal injury caused by UUO was evaluated by histopathology and analysis of gene expression, oxidative stress, intracellular organelles, apoptosis, and Wnt3α/β-catenin/GSK-3β signaling·H2O2-exposed human kidney (HK-2) cells were also examined after treatment with CoQ10 or an RIP inhibitor.

RESULTS: UUO induced marked renal tubular necrosis, upregulation of RIP1-RIP3-MLKL axis proteins, activation of the NLRP3 inflammasome, and evolution of renal fibrosis. UUO-induced oxidative stress evoked excessive endoplasmic reticulum stress and mitochondrial dysfunction, which triggered apoptotic cell death through Wnt3α/β-catenin/GSK-3β signaling. All of these effects were mitigated by CoQ10 or an RIP inhibitor. In H2O2-treated HK-2 cells, CoQ10 or an RIP inhibitor suppressed the expression of RIP1-RIP3-MLKL proteins and pyroptosis-related cytokines, and hindered the production of intracellular reactive oxygen species as shown by MitoSOX Red staining and apoptotic cell death but increased cell viability. The CoQ10 or Wnt/β-catenin inhibitor ICG-001 deactivated H2O2-stimulated activation of Wnt3α/β-catenin/GSK-3β signaling.

CONCLUSION: These findings suggest that CoQ10 attenuates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in UUO.}, } @article {pmid35633884, year = {2022}, author = {Zhang, L and Liu, K and Zhuan, Q and Liu, Z and Meng, L and Fu, X and Jia, G and Hou, Y}, title = {Mitochondrial Calcium Disorder Affects Early Embryonic Development in Mice through Regulating the ERK/MAPK Pathway.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {8221361}, pmid = {35633884}, issn = {1942-0994}, mesh = {Animals ; *Calcium/metabolism ; *Embryonic Development ; *MAP Kinase Signaling System ; Mice ; Mitochondria/metabolism ; *Mitogen-Activated Protein Kinases/metabolism ; Oocytes/metabolism ; }, abstract = {The homeostasis of mitochondrial calcium ([Ca[2+]]mt) in oocytes plays a critical role in maintaining normal reproductive cellular progress such as meiosis. However, little is known about the association between [Ca[2+]]mt homeostasis and early embryonic development. Two in vitro mouse MII oocyte models were established by using a specific agonist or inhibitor targeting mitochondrial calcium uniporters (MCU) to upregulate or downregulate [Ca[2+]]mt concentrations. The imbalance of [Ca[2+]]mt in MII oocytes causes mitochondrial dysfunction and morphological abnormity, leading to an abnormal spindle/chromosome structure. Oocytes in drug-treated groups are less likely to develop into blastocyst during in vitro culture. Abnormal [Ca[2+]]mt concentrations in oocytes hindered epigenetic modification and regulated mitogen-activated protein kinase (MAPK) signaling that is associated with gene expression. We also found that MAPK/ERK signaling is regulating DNA methylation in MII oocytes to modulate epigenetic modification. These data provide a new insight into the protective role of [Ca[2+]]mt homeostasis in early embryonic development and also demonstrate a new mechanism of MAPK signaling regulated by [Ca[2+]]mt that influences epigenetic modification.}, } @article {pmid35630799, year = {2022}, author = {Xie, DM and Zhang, Q and Xin, LK and Wang, GK and Liu, CB and Qin, MJ}, title = {Cloning and Functional Characterization of Two Germacrene A Oxidases Isolated from Xanthium sibiricum.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {10}, pages = {}, pmid = {35630799}, issn = {1420-3049}, mesh = {Cloning, Molecular ; Oxidoreductases/metabolism ; Phylogeny ; Plant Proteins/metabolism ; Sesquiterpenes, Germacrane ; *Xanthium/genetics ; }, abstract = {Sesquiterpene lactones (STLs) from the cocklebur Xanthium sibiricum exhibit significant anti-tumor activity. Although germacrene A oxidase (GAO), which catalyzes the production of Germacrene A acid (GAA) from germacrene A, an important precursor of germacrene-type STLs, has been reported, the remaining GAOs corresponding to various STLs' biosynthesis pathways remain unidentified. In this study, 68,199 unigenes were studied in a de novo transcriptome assembly of X. sibiricum fruits. By comparison with previously published GAO sequences, two candidate X. sibiricum GAO gene sequences, XsGAO1 (1467 bp) and XsGAO2 (1527 bp), were identified, cloned, and predicted to encode 488 and 508 amino acids, respectively. Their protein structure, motifs, sequence similarity, and phylogenetic position were similar to those of other GAO proteins. They were most strongly expressed in fruits, according to a quantitative real-time polymerase chain reaction (qRT-PCR), and both XsGAO proteins were localized in the mitochondria of tobacco leaf epidermal cells. The two XsGAO genes were cloned into the expression vector for eukaryotic expression in Saccharomyces cerevisiae, and the enzyme reaction products were detected by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) methods. The results indicated that both XsGAO1 and XsGAO2 catalyzed the two-step conversion of germacrene A (GA) to GAA, meaning they are unlike classical GAO enzymes, which catalyze a three-step conversion of GA to GAA. This cloning and functional study of two GAO genes from X. sibiricum provides a useful basis for further elucidation of the STL biosynthesis pathway in X. sibiricum.}, } @article {pmid35627195, year = {2022}, author = {Popadin, K and Gunbin, K and Peshkin, L and Annis, S and Fleischmann, Z and Franco, M and Kraytsberg, Y and Markuzon, N and Ackermann, RR and Khrapko, K}, title = {Mitochondrial Pseudogenes Suggest Repeated Inter-Species Hybridization among Direct Human Ancestors.}, journal = {Genes}, volume = {13}, number = {5}, pages = {}, pmid = {35627195}, issn = {2073-4425}, support = {R01-HD091439/NH/NIH HHS/United States ; }, mesh = {Animals ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; *Hominidae/genetics ; Humans ; Hybridization, Genetic ; Mitochondria/genetics ; *Pseudogenes/genetics ; }, abstract = {The hypothesis that the evolution of humans involves hybridization between diverged species has been actively debated in recent years. We present the following novel evidence in support of this hypothesis: the analysis of nuclear pseudogenes of mtDNA ("NUMTs"). NUMTs are considered "mtDNA fossils" as they preserve sequences of ancient mtDNA and thus carry unique information about ancestral populations. Our comparison of a NUMT sequence shared by humans, chimpanzees, and gorillas with their mtDNAs implies that, around the time of divergence between humans and chimpanzees, our evolutionary history involved the interbreeding of individuals whose mtDNA had diverged as much as ~4.5 Myr prior. This large divergence suggests a distant interspecies hybridization. Additionally, analysis of two other NUMTs suggests that such events occur repeatedly. Our findings suggest a complex pattern of speciation in primate/human ancestors and provide one potential explanation for the mosaic nature of fossil morphology found at the emergence of the hominin lineage. A preliminary version of this manuscript was uploaded to the preprint server BioRxiv in 2017 (10.1101/134502).}, } @article {pmid35626633, year = {2022}, author = {Eyenga, P and Rey, B and Eyenga, L and Sheu, SS}, title = {Regulation of Oxidative Phosphorylation of Liver Mitochondria in Sepsis.}, journal = {Cells}, volume = {11}, number = {10}, pages = {}, pmid = {35626633}, issn = {2073-4409}, mesh = {Adenosine Triphosphate/metabolism ; Electron Transport Complex IV/metabolism ; Humans ; Mitochondria, Liver/metabolism ; *Oxidative Phosphorylation ; *Sepsis/metabolism ; }, abstract = {The link between liver dysfunction and decreased mitochondrial oxidative phosphorylation in sepsis has been clearly established in experimental models. Energy transduction is plastic: the efficiency of mitochondrial coupling collapses in the early stage of sepsis but is expected to increase during the recovery phases of sepsis. Among the mechanisms regulating the coupling efficiency of hepatic mitochondria, the slipping reactions at the cytochrome oxidase and ATP synthase seem to be a determining element, whereas other regulatory mechanisms such as those involving proton leakage across the mitochondrial membrane have not yet been formally proven in the context of sepsis. If the dysfunction of hepatic mitochondria is related to impaired cytochrome c oxidase and ATP synthase functions, we need to consider therapeutic avenues to restore their activities for recovery from sepsis. In this review, we discussed previous findings regarding the regulatory mechanism involved in changes in the oxidative phosphorylation of liver mitochondria in sepsis, and propose therapeutic avenues to improve the functions of cytochrome c oxidase and ATP synthase in sepsis.}, } @article {pmid35614856, year = {2022}, author = {Xu, JJ and Hu, M and Yang, L and Chen, XY}, title = {How plants synthesize coenzyme Q.}, journal = {Plant communications}, volume = {3}, number = {5}, pages = {100341}, pmid = {35614856}, issn = {2590-3462}, mesh = {Mitochondria/metabolism ; Oxidation-Reduction ; *Plants/genetics/metabolism ; *Ubiquinone/metabolism ; }, abstract = {Coenzyme Q (CoQ) is a conserved redox-active lipid that has a wide distribution across the domains of life. CoQ plays a key role in the oxidative electron transfer chain and serves as a crucial antioxidant in cellular membranes. Our understanding of CoQ biosynthesis in eukaryotes has come mostly from studies of yeast. Recently, significant advances have been made in understanding CoQ biosynthesis in plants. Unique mitochondrial flavin-dependent monooxygenase and benzenoid ring precursor biosynthetic pathways have been discovered, providing new insights into the diversity of CoQ biosynthetic pathways and the evolution of phototrophic eukaryotes. We summarize research progress on CoQ biosynthesis and regulation in plants and recent efforts to increase the CoQ content in plant foods.}, } @article {pmid35609548, year = {2022}, author = {Schärer, L}, title = {Evolution: Mitochondrial lodgers can take over in hermaphroditic snails.}, journal = {Current biology : CB}, volume = {32}, number = {10}, pages = {R477-R479}, doi = {10.1016/j.cub.2022.04.039}, pmid = {35609548}, issn = {1879-0445}, mesh = {Animals ; Cytoplasm ; *Hermaphroditic Organisms ; *Mitochondria ; *Snails ; }, abstract = {Mitochondria - the cell's power stations - are inherited uniparentally via eggs, not sperm. In hermaphroditic plants, they sometimes prevent their hosts from making pollen (and sperm), causing cytoplasmic male sterility. New evidence from a hermaphroditic freshwater snail now documents cytoplasmic male sterility in animals.}, } @article {pmid35596716, year = {2022}, author = {Yu, G and Nakajima, K and Gruber, A and Rio Bartulos, C and Schober, AF and Lepetit, B and Yohannes, E and Matsuda, Y and Kroth, PG}, title = {Mitochondrial phosphoenolpyruvate carboxylase contributes to carbon fixation in the diatom Phaeodactylum tricornutum at low inorganic carbon concentrations.}, journal = {The New phytologist}, volume = {235}, number = {4}, pages = {1379-1393}, doi = {10.1111/nph.18268}, pmid = {35596716}, issn = {1469-8137}, mesh = {Bicarbonates/metabolism ; Carbon/metabolism ; Carbon Cycle ; Carbon Dioxide/metabolism/pharmacology ; Dacarbazine/metabolism ; *Diatoms/metabolism ; Mitochondria/metabolism ; Phosphoenolpyruvate Carboxylase/genetics/metabolism ; Photosynthesis ; }, abstract = {Photosynthetic carbon fixation is often limited by CO2 availability, which led to the evolution of CO2 concentrating mechanisms (CCMs). Some diatoms possess CCMs that employ biochemical fixation of bicarbonate, similar to C4 plants, but whether biochemical CCMs are commonly found in diatoms is a subject of debate. In the diatom Phaeodactylum tricornutum, phosphoenolpyruvate carboxylase (PEPC) is present in two isoforms, PEPC1 in the plastids and PEPC2 in the mitochondria. We used real-time quantitative polymerase chain reaction, Western blots, and enzymatic assays to examine PEPC expression and PEPC activity, under low and high concentrations of dissolved inorganic carbon (DIC). We generated and analyzed individual knockout cell lines of PEPC1 and PEPC2, as well as a PEPC1/2 double-knockout strain. While we could not detect an altered phenotype in the PEPC1 knockout strains at ambient, low or high DIC concentrations, PEPC2 and the double-knockout strains grown under ambient air or lower DIC availability conditions showed reduced growth and photosynthetic affinity for DIC while behaving similarly to wild-type (WT) cells at high DIC concentrations. These mutants furthermore exhibited significantly lower [13] C/[12] C ratios compared to the WT. Our data imply that in P. tricornutum at least parts of the CCM rely on biochemical bicarbonate fixation catalyzed by the mitochondrial PEPC2.}, } @article {pmid35588086, year = {2022}, author = {Santos, HJ and Nozaki, T}, title = {The mitosome of the anaerobic parasitic protist Entamoeba histolytica: A peculiar and minimalist mitochondrion-related organelle.}, journal = {The Journal of eukaryotic microbiology}, volume = {69}, number = {6}, pages = {e12923}, doi = {10.1111/jeu.12923}, pmid = {35588086}, issn = {1550-7408}, mesh = {Humans ; Anaerobiosis ; *Entamoeba histolytica/metabolism ; Membrane Proteins/metabolism ; *Mitochondria/metabolism ; *Organelles/metabolism ; }, abstract = {The simplest class of mitochondrion-related organelles (MROs) is the mitosome, an organelle present in a few anaerobic protozoan parasites such as Entamoeba histolytica, Giardia intestinalis, and Cryptosporidium parvum. E. histolytica causes amoebiasis in humans, deemed as one of the important, yet neglected tropical infections in the world. Much of the enigma of the E. histolytica mitosome circles around the obvious lack of a majority of known mitochondrial components and functions exhibited in other organisms. The identification of enzymes responsible for sulfate activation (AS, IPP, and APSK) and a number of lineage-specific proteins such as the outer membrane beta-barrel protein (MBOMP30), and transmembrane domain-containing proteins that bind to various organellar proteins (ETMP1, ETMP30, EHI_170120, and EHI_099350) showcased the remarkable divergence of this organelle compared to the other MROs of anaerobic protozoa. Here, we summarize the findings regarding the biology of the mitosomes in E. histolytica, from their discovery up to the present understanding of its roles and interactions. We also include current advances and future perspectives on the biology, biochemistry, and evolution of the mitosomes of E. histolytica.}, } @article {pmid35587988, year = {2022}, author = {Huynen, MA and Elurbe, DM}, title = {Mitochondrial complex complexification.}, journal = {Science (New York, N.Y.)}, volume = {376}, number = {6595}, pages = {794-795}, doi = {10.1126/science.abq0368}, pmid = {35587988}, issn = {1095-9203}, mesh = {*Electron Transport Complex I/chemistry/genetics ; *Electron Transport Complex IV/chemistry/genetics ; Evolution, Molecular ; *Mitochondria/enzymology ; Oxidative Phosphorylation ; Protein Subunits/chemistry/genetics ; *Tetrahymena thermophila/enzymology ; }, abstract = {Variation in complex composition provides clues about the function of individual subunits.}, } @article {pmid35585601, year = {2022}, author = {Vujovic, F and Hunter, N and Farahani, RM}, title = {Notch ankyrin domain: evolutionary rise of a thermodynamic sensor.}, journal = {Cell communication and signaling : CCS}, volume = {20}, number = {1}, pages = {66}, pmid = {35585601}, issn = {1478-811X}, mesh = {Animals ; *Ankyrins/chemistry/metabolism ; Mice ; *Neural Stem Cells/chemistry/metabolism ; Phylogeny ; Protein Domains ; *Receptors, Notch/chemistry/metabolism ; Signal Transduction ; Thermodynamics ; }, abstract = {Notch signalling pathway plays a key role in metazoan biology by contributing to resolution of binary decisions in the life cycle of cells during development. Outcomes such as proliferation/differentiation dichotomy are resolved by transcriptional remodelling that follows a switch from Notch[on] to Notch[off] state, characterised by dissociation of Notch intracellular domain (NICD) from DNA-bound RBPJ. Here we provide evidence that transitioning to the Notch[off] state is regulated by heat flux, a phenomenon that aligns resolution of fate dichotomies to mitochondrial activity. A combination of phylogenetic analysis and computational biochemistry was utilised to disclose structural adaptations of Notch1 ankyrin domain that enabled function as a sensor of heat flux. We then employed DNA-based micro-thermography to measure heat flux during brain development, followed by analysis in vitro of the temperature-dependent behaviour of Notch1 in mouse neural progenitor cells. The structural capacity of NICD to operate as a thermodynamic sensor in metazoans stems from characteristic enrichment of charged acidic amino acids in β-hairpins of the ankyrin domain that amplify destabilising inter-residue electrostatic interactions and render the domain thermolabile. The instability emerges upon mitochondrial activity which raises the perinuclear and nuclear temperatures to 50 °C and 39 °C, respectively, leading to destabilization of Notch1 transcriptional complex and transitioning to the Notch[off] state. Notch1 functions a metazoan thermodynamic sensor that is switched on by intercellular contacts, inputs heat flux as a proxy for mitochondrial activity in the Notch[on] state via the ankyrin domain and is eventually switched off in a temperature-dependent manner. Video abstract.}, } @article {pmid35584780, year = {2022}, author = {da Silva E Silva, LH and da Silva, FS and Medeiros, DBA and Cruz, ACR and da Silva, SP and Aragão, AO and Dias, DD and Sena do Nascimento, BL and Júnior, JWR and Vieira, DBR and Monteiro, HAO and Neto, JPN}, title = {Description of the mitogenome and phylogeny of Aedes spp. (Diptera: Culicidae) from the Amazon region.}, journal = {Acta tropica}, volume = {232}, number = {}, pages = {106500}, doi = {10.1016/j.actatropica.2022.106500}, pmid = {35584780}, issn = {1873-6254}, mesh = {*Aedes ; Animals ; *Culicidae/genetics ; *Genome, Mitochondrial/genetics ; Mosquito Vectors/genetics ; Phylogeny ; *Zika Virus/genetics ; *Zika Virus Infection ; }, abstract = {The genus Aedes (Diptera: Culicidae) includes species of great epidemiological relevance, particularly involved in transmission cycles of leading arboviruses in the Brazilian Amazon region, such as the Zika virus (ZIKV), Dengue virus (DENV), Yellow fever virus (YFV), and Chikungunya virus (CHIKV). We report here the first putatively complete sequencing of the mitochondrial genomes of Brazilian populations of the species Aedes albopictus, Aedes scapularis and Aedes serratus. The sequences obtained showed an average length of 14,947 bp, comprising 37 functional subunits, typical in animal mitochondria (13 PCGs, 22 tRNA, and 2 rRNA). The phylogeny reconstructed by Maximum likelihood method, based on the concatenated sequences of all 13 PCGs produced at least two non-directly related groupings, composed of representatives of the subgenus Ochlerotatus and Stegomyia of the genus Aedes. The data and information produced here may be useful for future taxonomic and evolutionary studies of the genus Aedes, as well as the Culicidae family.}, } @article {pmid35580923, year = {2022}, author = {Maldonado, JA and Firneno, TJ and Hall, AS and Fujita, MK}, title = {Parthenogenesis doubles the rate of amino acid substitution in whiptail mitochondria.}, journal = {Evolution; international journal of organic evolution}, volume = {76}, number = {7}, pages = {1434-1442}, doi = {10.1111/evo.14509}, pmid = {35580923}, issn = {1558-5646}, mesh = {Amino Acid Substitution ; *Genome, Mitochondrial ; Humans ; Male ; Mitochondria/genetics ; Mutation ; Parthenogenesis/genetics ; Phylogeny ; *Reproduction, Asexual/genetics ; }, abstract = {Sexual reproduction is ubiquitous in the natural world, suggesting that sex must have extensive benefits to overcome the cost of males compared to asexual reproduction. One hypothesized advantage of sex with strong theoretical support is that sex plays a role in removing deleterious mutations from the genome. Theory predicts that transitions to asexuality should lead to the suppression of recombination and segregation and, in turn, weakened natural selection, allowing for the accumulation of slightly deleterious mutations. We tested this prediction by estimating the dN/dS ratios in asexual vertebrate lineages in the genus Aspidoscelis using whole mitochondrial genomes from seven asexual and five sexual species. We found higher dN/dS ratios in asexual Aspidoscelis species, indicating that asexual whiptails accumulate nonsynonymous substitutions due to weaker purifying selection. Additionally, we estimated nucleotide diversity and found that asexuals harbor significantly less diversity. Thus, despite their recent origins, slightly deleterious mutations accumulated rapidly enough in asexual lineages to be detected. We provide empirical evidence to corroborate the connection between asexuality and increased amino acid substitutions in asexual vertebrate lineages.}, } @article {pmid35580797, year = {2022}, author = {Sandamalika, WMG and Udayantha, HMV and Liyanage, DS and Lim, C and Kim, G and Kwon, H and Lee, J}, title = {Identification of reactive oxygen species modulator 1 (Romo 1) from black rockfish (Sebastes schlegelii) and deciphering its molecular characteristics, immune responses, oxidative stress modulation, and wound healing properties.}, journal = {Fish & shellfish immunology}, volume = {125}, number = {}, pages = {266-275}, doi = {10.1016/j.fsi.2022.05.026}, pmid = {35580797}, issn = {1095-9947}, mesh = {Amino Acid Sequence ; Animals ; *Bass ; DNA, Complementary/genetics ; Female ; Fish Proteins/chemistry ; Immunity, Innate/genetics ; Lipopolysaccharides/metabolism/pharmacology ; Male ; Mammals/genetics/metabolism ; Oxidative Stress ; *Perciformes ; Phylogeny ; Reactive Oxygen Species ; Sequence Alignment ; Wound Healing ; }, abstract = {Reactive oxygen species modulator 1 (Romo1) is a mitochondrial inner membrane protein that induces mitochondrial reactive oxygen species (ROS) generation. In this study, we identified the Romo1 homolog from the black rockfish (Sebastes schlegelii), named it as SsRomo1, and characterized it at the molecular as well as functional levels. An open reading frame consisting of 240 bp was identified in the SsRomo1 complementary DNA (cDNA) sequence that encodes a 79 amino acid-long polypeptide with a molecular weight of 8,293 Da and a theoretical isoelectric point (pI) of 9.89. The in silico analysis revealed the characteristic features of SsRomo1, namely the presence of a transmembrane domain and the lack of a signal peptide. Homology analysis revealed that SsRomo1 exhibits the highest sequence identity with its fish counterparts (>93%) and shares a similar percentage of sequence identity with mammals (>92%). Additionally, it is closely clustered together with the fish clade in the constructed phylogenetic tree. The subcellular localization analysis confirmed its mitochondrial localization within the fathead minnow (FHM) cells. Under normal physiological conditions, the SsRomo1 mRNA is highly expressed in the rockfish ovary, followed by the blood and testis, indicating the abundance of mitochondria in these tissues. Furthermore, the significant upregulation of SsRomo1 in cells treated with lipopolysachharide (LPS), polyinosinic:polycytidylic acid, and Streptococcus iniae suggest that the increased ROS production is induced by SsRomo1 to eliminate pathogens during infections. Incidentally, we believe that this study is the first to determine the involvement of SsRomo1 in LPS-mediated nitric oxide (NO) production in RAW267.4 cells, based on their higher NO production as compared to that in the control. Moreover, overexpression of SsRomo1 enhanced the wound healing ability of FHM cells, indicating its high invasion and migration properties. We also determined the hydrogen peroxide-mediated cell viability of SsRomo1-overexpressed FHM cells and observed a significant reduction in viability, which is possibly due to increased ROS production. Collectively, our observations suggest that SsRomo1 plays an important role in oxidative stress modulation upon immune stimulation and in maintenance of tissue homeostasis in black rockfish.}, } @article {pmid35577958, year = {2022}, author = {Bates, M and Keller-Findeisen, J and Przybylski, A and Hüper, A and Stephan, T and Ilgen, P and Cereceda Delgado, AR and D'Este, E and Egner, A and Jakobs, S and Sahl, SJ and Hell, SW}, title = {Optimal precision and accuracy in 4Pi-STORM using dynamic spline PSF models.}, journal = {Nature methods}, volume = {19}, number = {5}, pages = {603-612}, pmid = {35577958}, issn = {1548-7105}, mesh = {Animals ; Artifacts ; *Lenses ; Mammals ; Microscopy ; Optical Imaging ; *Single Molecule Imaging ; }, abstract = {Coherent fluorescence imaging with two objective lenses (4Pi detection) enables single-molecule localization microscopy with sub-10 nm spatial resolution in three dimensions. Despite its outstanding sensitivity, wider application of this technique has been hindered by complex instrumentation and the challenging nature of the data analysis. Here we report the development of a 4Pi-STORM microscope, which obtains optimal resolution and accuracy by modeling the 4Pi point spread function (PSF) dynamically while also using a simpler optical design. Dynamic spline PSF models incorporate fluctuations in the modulation phase of the experimentally determined PSF, capturing the temporal evolution of the optical system. Our method reaches the theoretical limits for precision and minimizes phase-wrapping artifacts by making full use of the information content of the data. 4Pi-STORM achieves a near-isotropic three-dimensional localization precision of 2-3 nm, and we demonstrate its capabilities by investigating protein and nucleic acid organization in primary neurons and mammalian mitochondria.}, } @article {pmid35577294, year = {2022}, author = {Xu, X and Yu, L and Li, F and Wang, B and Liu, F and Li, D}, title = {Phylogenetic placement and species delimitation of the crab spider genus Phrynarachne (Araneae: Thomisidae) from China.}, journal = {Molecular phylogenetics and evolution}, volume = {173}, number = {}, pages = {107521}, doi = {10.1016/j.ympev.2022.107521}, pmid = {35577294}, issn = {1095-9513}, mesh = {Animals ; China ; Mitochondria/genetics ; Phylogeny ; *Spiders/genetics ; }, abstract = {Evolutionary biologists have long been fascinated by the striking resemblance to bird droppings of the sit-and-wait crab spiders of the genus Phrynarachne. In doing so, species of Phrynarachne have evolved not to avoid detection, but rather, to cause predators to misidentify them as inedible and/or inanimate bird droppings. However, the lack of a phylogeny for Phrynarachne impedes our understanding of the evolution of this trait in the genus. Here we explore species boundaries in species of Phrynarachne from China using single- and multi-locus species delimitation approaches based on 30 Phrynarachne samples. All species delimitation approaches supported six species of Phrynarachne in China. We further present the first phylogenetic analysis of the genus Phrynarachne and estimate divergence times using two mitochondrial and three nuclear genes. All of our phylogenetic analyses supported the monophyly of Phrynarachne in China, with the genus still included within the higher 'Thomisus group' based on our results. Our dating analyses place the crown age of Phrynarachne in China to the middle Miocene. Taken together, our study provides a time-calibrated phylogeny of the genus Phrynarachne in China for testing hypotheses regarding the evolution of the lineage and bird dropping masquerade.}, } @article {pmid35575078, year = {2022}, author = {Lee, J and Willett, CS}, title = {Frequent Paternal Mitochondrial Inheritance and Rapid Haplotype Frequency Shifts in Copepod Hybrids.}, journal = {The Journal of heredity}, volume = {113}, number = {2}, pages = {171-183}, doi = {10.1093/jhered/esab068}, pmid = {35575078}, issn = {1465-7333}, mesh = {Animals ; *Copepoda/genetics ; DNA, Mitochondrial/genetics ; Genes, Mitochondrial ; Haplotypes ; Mitochondria/genetics ; Phylogeny ; }, abstract = {Mitochondria are assumed to be maternally inherited in most animal species, and this foundational concept has fostered advances in phylogenetics, conservation, and population genetics. Like other animals, mitochondria were thought to be solely maternally inherited in the marine copepod Tigriopus californicus, which has served as a useful model for studying mitonuclear interactions, hybrid breakdown, and environmental tolerance. However, we present PCR, Sanger sequencing, and Illumina Nextera sequencing evidence that extensive paternal mitochondrial DNA (mtDNA) transmission is occurring in inter-population hybrids of T. californicus. PCR on four types of crosses between three populations (total sample size of 376 F1 individuals) with 20% genome-wide mitochondrial divergence showed 2% to 59% of F1 hybrids with both paternal and maternal mtDNA, where low and high paternal leakage values were found in different cross directions of the same population pairs. Sequencing methods further verified nucleotide similarities between F1 mtDNA and paternal mtDNA sequences. Interestingly, the paternal mtDNA in F1s from some crosses inherited haplotypes that were uncommon in the paternal population. Compared to some previous research on paternal leakage, we employed more rigorous methods to rule out contamination and false detection of paternal mtDNA due to non-functional nuclear mitochondrial DNA fragments. Our results raise the potential that other animal systems thought to only inherit maternal mitochondria may also have paternal leakage, which would then affect the interpretation of past and future population genetics or phylogenetic studies that rely on mitochondria as uniparental markers.}, } @article {pmid35563133, year = {2022}, author = {Bonturi, CR and Silva Teixeira, AB and Rocha, VM and Valente, PF and Oliveira, JR and Filho, CMB and Fátima Correia Batista, I and Oliva, MLV}, title = {Plant Kunitz Inhibitors and Their Interaction with Proteases: Current and Potential Pharmacological Targets.}, journal = {International journal of molecular sciences}, volume = {23}, number = {9}, pages = {}, pmid = {35563133}, issn = {1422-0067}, mesh = {Endopeptidases ; Fungi/metabolism ; Humans ; *Plants/metabolism ; *Protease Inhibitors/chemistry/pharmacology/therapeutic use ; Serine Proteases/metabolism ; }, abstract = {The action of proteases can be controlled by several mechanisms, including regulation through gene expression; post-translational modifications, such as glycosylation; zymogen activation; targeting specific compartments, such as lysosomes and mitochondria; and blocking proteolysis using endogenous inhibitors. Protease inhibitors are important molecules to be explored for the control of proteolytic processes in organisms because of their ability to act on several proteases. In this context, plants synthesize numerous proteins that contribute to protection against attacks by microorganisms (fungi and bacteria) and/or invertebrates (insects and nematodes) through the inhibition of proteases in these organisms. These proteins are widely distributed in the plant kingdom, and are present in higher concentrations in legume seeds (compared to other organs and other botanical families), motivating studies on their inhibitory effects in various organisms, including humans. In most cases, the biological roles of these proteins have been assigned based mostly on their in vitro action, as is the case with enzyme inhibitors. This review highlights the structural evolution, function, and wide variety of effects of plant Kunitz protease inhibitors, and their potential for pharmaceutical application based on their interactions with different proteases.}, } @article {pmid35547863, year = {2021}, author = {Benz, R}, title = {Historical Perspective of Pore-Forming Activity Studies of Voltage-Dependent Anion Channel (Eukaryotic or Mitochondrial Porin) Since Its Discovery in the 70th of the Last Century.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {734226}, pmid = {35547863}, issn = {1664-042X}, abstract = {Eukaryotic porin, also known as Voltage-Dependent Anion Channel (VDAC), is the most frequent protein in the outer membrane of mitochondria that are responsible for cellular respiration. Mitochondria are most likely descendants of strictly aerobic Gram-negative bacteria from the α-proteobacterial lineage. In accordance with the presumed ancestor, mitochondria are surrounded by two membranes. The mitochondrial outer membrane contains besides the eukaryotic porins responsible for its major permeability properties a variety of other not fully identified channels. It encloses also the TOM apparatus together with the sorting mechanism SAM, responsible for the uptake and assembly of many mitochondrial proteins that are encoded in the nucleus and synthesized in the cytoplasm at free ribosomes. The recognition and the study of electrophysiological properties of eukaryotic porin or VDAC started in the late seventies of the last century by a study of Schein et al., who reconstituted the pore from crude extracts of Paramecium mitochondria into planar lipid bilayer membranes. Whereas the literature about structure and function of eukaryotic porins was comparatively rare during the first 10years after the first study, the number of publications started to explode with the first sequencing of human Porin 31HL and the recognition of the important function of eukaryotic porins in mitochondrial metabolism. Many genomes contain more than one gene coding for homologs of eukaryotic porins. More than 100 sequences of eukaryotic porins are known to date. Although the sequence identity between them is relatively low, the polypeptide length and in particular, the electrophysiological characteristics are highly preserved. This means that all eukaryotic porins studied to date are anion selective in the open state. They are voltage-dependent and switch into cation-selective substates at voltages in the physiological relevant range. A major breakthrough was also the elucidation of the 3D structure of the eukaryotic pore, which is formed by 19 β-strands similar to those of bacterial porin channels. The function of the presumed gate an α-helical stretch of 20 amino acids allowed further studies with respect to voltage dependence and function, but its exact role in channel gating is still not fully understood.}, } @article {pmid35543999, year = {2022}, author = {Corsaro, D}, title = {Insights into Microsporidia Evolution from Early Diverging Microsporidia.}, journal = {Experientia supplementum (2012)}, volume = {114}, number = {}, pages = {71-90}, pmid = {35543999}, issn = {1664-431X}, mesh = {Animals ; Fungi ; *Microsporidia/genetics ; *Parasites ; Phylogeny ; }, abstract = {Microsporidia have drastically modified genomes and cytology resulting from their high level of adaptation to intracytoplasmic parasitism. Their origins, which had long remained enigmatic, were placed within the line of Rozella, a primitive endoparasitic chytrid. These origins became more and more refined with the discovery of various parasites morphologically similar to the primitive lines of microsporidia (Metchnikovellids and Chytridiopsids) but which possess fungal-like genomes and functional mitochondria. These various parasites turn out to be distinct missing links between a large assemblage of chytrid-like rozellids and the true microsporidians, which are actually a very evolved branch of the rozellids themselves. The question of how to consider the historically known Microsporidia and the various microsporidia-like organisms within paraphyletic rozellids is discussed.}, } @article {pmid35508562, year = {2022}, author = {Kidd, KK and Evsanaa, B and Togtokh, A and Brissenden, JE and Roscoe, JM and Dogan, M and Neophytou, PI and Gurkan, C and Bulbul, O and Cherni, L and Speed, WC and Murtha, M and Kidd, JR and Pakstis, AJ}, title = {North Asian population relationships in a global context.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {7214}, pmid = {35508562}, issn = {2045-2322}, mesh = {*Asian People/genetics ; Ethnicity/genetics ; Genetic Variation ; *Genetics, Population ; Haplotypes ; Humans ; Phylogeny ; Principal Component Analysis ; }, abstract = {Population genetic studies of North Asian ethnic groups have focused on genetic variation of sex chromosomes and mitochondria. Studies of the extensive variation available from autosomal variation have appeared infrequently. We focus on relationships among population samples using new North Asia microhaplotype data. We combined genotypes from our laboratory on 58 microhaplotypes, distributed across 18 autosomes, on 3945 individuals from 75 populations with corresponding data extracted for 26 populations from the Thousand Genomes consortium and for 22 populations from the GenomeAsia 100 K project. A total of 7107 individuals in 122 total populations are analyzed using STRUCTURE, Principal Component Analysis, and phylogenetic tree analyses. North Asia populations sampled in Mongolia include: Buryats, Mongolians, Altai Kazakhs, and Tsaatans. Available Siberians include samples of Yakut, Khanty, and Komi Zyriane. Analyses of all 122 populations confirm many known relationships and show that most populations from North Asia form a cluster distinct from all other groups. Refinement of analyses on smaller subsets of populations reinforces the distinctiveness of North Asia and shows that the North Asia cluster identifies a region that is ancestral to Native Americans.}, } @article {pmid35504558, year = {2022}, author = {Zhou, W and Zhao, Z and Yu, Z and Hou, Y and Keerthiga, R and Fu, A}, title = {Mitochondrial transplantation therapy inhibits the proliferation of malignant hepatocellular carcinoma and its mechanism.}, journal = {Mitochondrion}, volume = {65}, number = {}, pages = {11-22}, doi = {10.1016/j.mito.2022.04.004}, pmid = {35504558}, issn = {1872-8278}, mesh = {Animals ; Apoptosis ; *Carcinoma, Hepatocellular/metabolism/pathology/therapy ; Cell Line, Tumor ; Cell Proliferation ; Female ; *Liver Neoplasms/metabolism/pathology/therapy ; Male ; Mice ; Mitochondria/metabolism ; }, abstract = {Mitochondrial dysfunction plays a vital role in growth and malignancy of tumors. In recent scenarios, mitochondrial transplantation therapy is considered as an effective method to remodel mitochondrial function in mitochondria-related diseases. However, the mechanism by which mitochondrial transplantation blocks tumor cell proliferation is still not determined. In addition, mitochondria are maternal inheritance in evolution, and mitochondria obtained from genders exhibit differences in mitochondrial activity. Therefore, the study indicates the inhibitory effect of mitochondria from different genders on hepatocellular carcinoma and explores the molecular mechanism. The results reveal that the healthy mitochondria can retard the proliferation of the hepatocellular carcinoma cells in vitro and in vivo through arresting cell cycle and inducing apoptosis. The molecular mechanism suggests that mitochondrial transplantation therapy can decrease aerobic glycolysis, and down-regulate the expression of cycle-related proteins while up-regulate apoptosis-related proteins in tumor cells. In addition, the antitumor activity of mitochondria from female mice (F-Mito) is relatively higher than that of mitochondria from male mice (M-Mito), which would be related to the evidence that the F-Mito process higher activity than the M-Mito. This study clarifies the mechanism of exogenous mitochondria inhibiting the proliferation of hepatocellular carcinoma and contributes a new biotechnology for therapy of mitochondria-related diseases from different genders.}, } @article {pmid35503755, year = {2022}, author = {Niu, Y and Lu, Y and Song, W and He, X and Liu, Z and Zheng, C and Wang, S and Shi, C and Liu, J}, title = {Assembly and comparative analysis of the complete mitochondrial genome of three Macadamia species (M. integrifolia, M. ternifolia and M. tetraphylla).}, journal = {PloS one}, volume = {17}, number = {5}, pages = {e0263545}, pmid = {35503755}, issn = {1932-6203}, mesh = {Genome Size ; *Genome, Chloroplast ; *Genome, Mitochondrial/genetics ; Genome, Plant ; Macadamia/genetics ; Phylogeny ; }, abstract = {BACKGROUND: Macadamia is a true dicotyledonous plant that thrives in a mild, humid, low wind environment. It is cultivated and traded internationally due to its high-quality nuts thus, has significant development prospects and scientific research value. However, information on the genetic resources of Macadamia spp. remains scanty.

RESULTS: The mitochondria (mt) genomes of three economically important Macadamia species, Macadamia integrifolia, M. ternifolia and M. tetraphylla, were assembled through the Illumina sequencing platform. The results showed that each species has 71 genes, including 42 protein-coding genes, 26 tRNAs, and 3 rRNAs. Repeated sequence analysis, RNA editing site prediction, and analysis of genes migrating from chloroplast (cp) to mt were performed in the mt genomes of the three Macadamia species. Phylogenetic analysis based on the mt genome of the three Macadamia species and 35 other species was conducted to reveal the evolution and taxonomic status of Macadamia. Furthermore, the characteristics of the plant mt genome, including genome size and GC content, were studied through comparison with 36 other plant species. The final non-synonymous (Ka) and synonymous (Ks) substitution analysis showed that most of the protein-coding genes in the mt genome underwent negative selections, indicating their importance in the mt genome.

CONCLUSION: The findings of this study provide a better understanding of the Macadamia genome and will inform future research on the genus.}, } @article {pmid35501686, year = {2022}, author = {Liu, H and Zhao, W and Hua, W and Liu, J}, title = {A large-scale population based organelle pan-genomes construction and phylogeny analysis reveal the genetic diversity and the evolutionary origins of chloroplast and mitochondrion in Brassica napus L.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {339}, pmid = {35501686}, issn = {1471-2164}, mesh = {Brassica/genetics ; *Brassica napus/genetics ; Brassica rapa/genetics ; Chloroplasts/genetics ; Genetic Variation ; *Genome, Chloroplast ; *Genome, Mitochondrial ; Genome, Plant ; Mitochondria/genetics ; Phylogeny ; }, abstract = {BACKGROUND: Allotetraploid oilseed rape (Brassica napus L.) is an important worldwide oil-producing crop. The origin of rapeseed is still undetermined due to the lack of wild resources. Despite certain genetic architecture and phylogenetic studies have been done focus on large group of Brassica nuclear genomes, the organelle genomes information under global pattern is largely unknown, which provide unique material for phylogenetic studies of B. napus. Here, based on de novo assemblies of 1,579 B. napus accessions collected globally, we constructed the chloroplast and mitochondrial pan-genomes of B. napus, and investigated the genetic diversity, phylogenetic relationships of B. napus, B. rapa and B. oleracea.

RESULTS: Based on mitotype-specific markers and mitotype-variant ORFs, four main cytoplasmic haplotypes were identified in our groups corresponding the nap, pol, ole, and cam mitotypes, among which the structure of chloroplast genomes was more conserved without any rearrangement than mitochondrial genomes. A total of 2,092 variants were detected in chloroplast genomes, whereas only 326 in mitochondrial genomes, indicating that chloroplast genomes exhibited a higher level of single-base polymorphism than mitochondrial genomes. Based on whole-genome variants diversity analysis, eleven genetic difference regions among different cytoplasmic haplotypes were identified on chloroplast genomes. The phylogenetic tree incorporating accessions of the B. rapa, B. oleracea, natural and synthetic populations of B. napus revealed multiple origins of B. napus cytoplasm. The cam-type and pol-type were both derived from B. rapa, while the ole-type was originated from B. oleracea. Notably, the nap-type cytoplasm was identified in both the B. rapa population and the synthetic B. napus, suggesting that B. rapa might be the maternal ancestor of nap-type B. napus.

CONCLUSIONS: The phylogenetic results provide novel insights into the organelle genomic evolution of Brassica species. The natural rapeseeds contained at least four cytoplastic haplotypes, of which the predominant nap-type might be originated from B. rapa. Besides, the organelle pan-genomes and the overall variation data offered useful resources for analysis of cytoplasmic inheritance related agronomical important traits of rapeseed, which can substantially facilitate the cultivation and improvement of rapeseed varieties.}, } @article {pmid35490656, year = {2022}, author = {Das, R and Kumar, A and Dalai, R and Goswami, C}, title = {Cytochrome C interacts with the pathogenic mutational hotspot region of TRPV4 and forms complexes that differ in mutation and metal ion-sensitive manner.}, journal = {Biochemical and biophysical research communications}, volume = {611}, number = {}, pages = {172-178}, doi = {10.1016/j.bbrc.2022.04.066}, pmid = {35490656}, issn = {1090-2104}, mesh = {*Cytochromes c/genetics/metabolism ; Ions/metabolism ; Mutation ; *TRPV Cation Channels/metabolism ; }, abstract = {The importance of TRPV4 in physiology and disease has been reported by several groups. Recently we have reported that TRPV4 localizes in the mitochondria in different cellular systems, regulates mitochondrial metabolism and electron transport chain functions. Here, we show that TRPV4 colocalizes with Cytochrome C (Cyt C), both in resting as well as in activated conditions. Amino acid region 592-630 of TRPV4 (termed as Fr592-630) that also covers TM4-Loop-TM5 region (which is also a hotspot of several pathogenic mutations) interacts with Cyt C, in a Ca[2+]-sensitive manner. This interaction is also variable and sensitive to other divalent and trivalent cations (i.e., Cu[2+], Mn[2+], Ni[2+], Zn[2+], Fe[3+]). Key residues of TRPV4 involved in these interactions remain conserved throughout the vertebrate evolution. Accordingly, this interaction is variable in the case of different pathogenic mutations (R616Q, F617L, L618P, V620I). Our data suggest that the TRPV4-Cyt C complex differs due to different mutations and is sensitive to the presence of different metal ions. We propose that TRPV4-Cyt C complex formation is important for physiological functions and relevant for TRPV4-induced channelopathies.}, } @article {pmid35483362, year = {2022}, author = {David, P and Degletagne, C and Saclier, N and Jennan, A and Jarne, P and Plénet, S and Konecny, L and François, C and Guéguen, L and Garcia, N and Lefébure, T and Luquet, E}, title = {Extreme mitochondrial DNA divergence underlies genetic conflict over sex determination.}, journal = {Current biology : CB}, volume = {32}, number = {10}, pages = {2325-2333.e6}, doi = {10.1016/j.cub.2022.04.014}, pmid = {35483362}, issn = {1879-0445}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; Evolution, Molecular ; Female ; *Genome, Mitochondrial ; Haplotypes ; Mitochondria/genetics ; }, abstract = {Cytoplasmic male sterility (CMS) is a form of genetic conflict over sex determination that results from differences in modes of inheritance between genomic compartments.[1-3] Indeed, maternally transmitted (usually mitochondrial) genes sometimes enhance their transmission by suppressing the male function in a hermaphroditic organism to the detriment of biparentally inherited nuclear genes. Therefore, these hermaphrodites become functionally female and may coexist with regular hermaphrodites in so-called gynodioecious populations.[3] CMS has been known in plants since Darwin's times[4] but is previously unknown in the animal kingdom.[5-8] We relate the first observation of CMS in animals. It occurs in a freshwater snail population, where some individuals appear unable to sire offspring in controlled crosses and show anatomical, physiological, and behavioral characters consistent with a suppression of the male function. Male sterility is associated with a mitochondrial lineage that underwent a spectacular acceleration of DNA substitution rates, affecting the entire mitochondrial genome-this acceleration concerns both synonymous and non-synonymous substitutions and therefore results from increased mitogenome mutation rates. Consequently, mitochondrial haplotype divergence within the population is exceptionally high, matching that observed between snail taxa that diverged 475 million years ago. This result is reminiscent of similar accelerations in mitogenome evolution observed in plant clades where gynodioecy is frequent,[9][,][10] both being consistent with arms-race evolution of genome regions implicated in CMS.[11][,][12] Our study shows that genomic conflicts can trigger independent evolution of similar sex-determination systems in plants and animals and dramatically accelerate molecular evolution.}, } @article {pmid35480047, year = {2022}, author = {De Pinto, V and Mahalakshmi, R and Messina, A}, title = {Editorial: VDAC Structure and Function: An Up-to-Date View.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {871586}, pmid = {35480047}, issn = {1664-042X}, support = {IA/S/20/2/505182/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, } @article {pmid35463435, year = {2022}, author = {Yi, L and Liu, B and Nixon, PJ and Yu, J and Chen, F}, title = {Recent Advances in Understanding the Structural and Functional Evolution of FtsH Proteases.}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {837528}, pmid = {35463435}, issn = {1664-462X}, abstract = {The FtsH family of proteases are membrane-anchored, ATP-dependent, zinc metalloproteases. They are universally present in prokaryotes and the mitochondria and chloroplasts of eukaryotic cells. Most bacteria bear a single ftsH gene that produces hexameric homocomplexes with diverse house-keeping roles. However, in mitochondria, chloroplasts and cyanobacteria, multiple FtsH homologs form homo- and heterocomplexes with specialized functions in maintaining photosynthesis and respiration. The diversification of FtsH homologs combined with selective pairing of FtsH isomers is a versatile strategy to enable functional adaptation. In this article we summarize recent progress in understanding the evolution, structure and function of FtsH proteases with a focus on the role of FtsH in photosynthesis and respiration.}, } @article {pmid35460877, year = {2022}, author = {Kodagoda, YK and Liyanage, DS and Omeka, WKM and Kwon, H and Hwang, SD and Lee, J}, title = {Molecular characterization, expression, and functional analysis of cystatin B in the big-belly seahorse (Hippocampus abdominalis).}, journal = {Fish & shellfish immunology}, volume = {124}, number = {}, pages = {442-453}, doi = {10.1016/j.fsi.2022.04.020}, pmid = {35460877}, issn = {1095-9947}, mesh = {Animals ; *Cyprinidae/genetics ; Cystatin B/genetics ; *Cystatins/genetics ; *Fish Diseases ; Fish Proteins/chemistry ; Male ; Phylogeny ; Poly I-C/pharmacology ; Sequence Alignment ; *Smegmamorpha ; }, abstract = {Cystatins are a diverse group of cysteine protease inhibitors widely present among various organisms. Beyond their protease inhibitor function, cystatins play a crucial role in diverse pathophysiological conditions in animals, including neurodegenerative disorders, tumor progression, inflammatory diseases, and immune response. However, the role of cystatins in immunity against viral and bacterial infections in fish remains to be elucidated. In this study, the cystatin B from big-belly seahorse, Hippocampus abdominalis, designated as HaCSTB, was identified and characterized. HaCSTB shared the highest homology with type 1 cystatin family members of teleosts and had three cystatin catalytic domains with no signal peptides or disulfide bonds. HaCSTB transcripts were mainly expressed in peripheral blood cells (PBCs), followed by the testis and pouch of healthy big-belly seahorses. Immune challenge with lipopolysaccharides (LPS), polyinosinic:polycytidylic acid (Poly I:C), and Streptococcus iniae induced upregulation of relative HaCSTB mRNA expression in PBCs. Subcellular localization analysis revealed the distribution of HaCSTB in the cytosol, mitochondria, and nuclei of fathead minnow cells (FHM). Recombinant HaCSTB (rHaCSTB) exhibited potent in vitro inhibitory activity against papain, a cysteine protease, in a concentration-, pH-, and temperature-dependent manner. Overexpression of HaCSTB in viral hemorrhagic septicemia virus (VHSV)-susceptible FHM cells increased cell viability and reduced VHSV-induced apoptosis. Collectively, these results suggest that HaCSTB might engage in the teleostean immune protection against bacteria and viruses.}, } @article {pmid35460575, year = {2022}, author = {Liu, Q and Iqbal, MF and Yaqub, T and Firyal, S and Zhao, Y and Stoneking, M and Li, M}, title = {The transmission of human mitochondrial DNA in four-generation pedigrees.}, journal = {Human mutation}, volume = {43}, number = {9}, pages = {1259-1267}, doi = {10.1002/humu.24390}, pmid = {35460575}, issn = {1098-1004}, mesh = {*DNA, Mitochondrial/genetics ; Humans ; Mitochondria/genetics ; *Mitochondrial Diseases/genetics ; Pedigree ; Selection, Genetic ; }, abstract = {Most of the pathogenic variants in mitochondrial DNA (mtDNA) exist in a heteroplasmic state (coexistence of mutant and wild-type mtDNA). Understanding how mtDNA is transmitted is crucial for predicting mitochondrial disease risk. Previous studies were based mainly on two-generation pedigree data, which are limited by the randomness in a single transmission. In this study, we analyzed the transmission of heteroplasmies in 16 four-generation families. First, we found that 57.8% of the variants in the great grandmother were transmitted to the fourth generation. The direction and magnitude of the frequency change during transmission appeared to be random. Moreover, no consistent correlation was identified between the frequency changes among the continuous transmissions, suggesting that most variants were functionally neutral or mildly deleterious and thus not subject to strong natural selection. Additionally, we found that the frequency of one nonsynonymous variant (m.15773G>A) showed a consistent increase in one family, suggesting that this variant may confer a fitness advantage to the mitochondrion/cell. We also estimated the effective bottleneck size during transmission to be 21-71. In summary, our study demonstrates the advantages of multigeneration data for studying the transmission of mtDNA for shedding new light on the dynamics of the mutation frequency in successive generations.}, } @article {pmid35457201, year = {2022}, author = {Juskeviciene, R and Fritz, AK and Brilkova, M and Akbergenov, R and Schmitt, K and Rehrauer, H and Laczko, E and Isnard-Petit, P and Thiam, K and Eckert, A and Schacht, J and Wolfer, DP and Böttger, EC and Shcherbakov, D}, title = {Phenotype of Mrps5-Associated Phylogenetic Polymorphisms Is Intimately Linked to Mitoribosomal Misreading.}, journal = {International journal of molecular sciences}, volume = {23}, number = {8}, pages = {}, pmid = {35457201}, issn = {1422-0067}, mesh = {Animals ; Mice ; *Mitochondrial Proteins/genetics ; Mutation ; Phenotype ; Phylogeny ; Protein Biosynthesis ; *Ribosomal Proteins/genetics ; }, abstract = {We have recently identified point mutation V336Y in mitoribosomal protein Mrps5 (uS5m) as a mitoribosomal ram (ribosomal ambiguity) mutation conferring error-prone mitochondrial protein synthesis. In vivo in transgenic knock-in animals, homologous mutation V338Y was associated with a discrete phenotype including impaired mitochondrial function, anxiety-related behavioral alterations, enhanced susceptibility to noise-induced hearing damage, and accelerated metabolic aging in muscle. To challenge the postulated link between Mrps5 V338Y-mediated misreading and the in vivo phenotype, we introduced mutation G315R into the mouse Mrps5 gene as Mrps5 G315R is homologous to the established bacterial ram mutation RpsE (uS5) G104R. However, in contrast to bacterial translation, the homologous G → R mutation in mitoribosomal Mrps5 did not affect the accuracy of mitochondrial protein synthesis. Importantly, in the absence of mitochondrial misreading, homozygous mutant MrpS5[G315R/G315R] mice did not show a phenotype distinct from wild-type animals.}, } @article {pmid35453648, year = {2022}, author = {Russo, C and Valle, MS and Casabona, A and Spicuzza, L and Sambataro, G and Malaguarnera, L}, title = {Vitamin D Impacts on Skeletal Muscle Dysfunction in Patients with COPD Promoting Mitochondrial Health.}, journal = {Biomedicines}, volume = {10}, number = {4}, pages = {}, pmid = {35453648}, issn = {2227-9059}, abstract = {Skeletal muscle dysfunction is frequently associated with chronic obstructive pulmonary disease (COPD), which is characterized by a permanent airflow limitation, with a worsening respiratory disorder during disease evolution. In COPD, the pathophysiological changes related to the chronic inflammatory state affect oxidant-antioxidant balance, which is one of the main mechanisms accompanying extra-pulmonary comorbidity such as muscle wasting. Muscle impairment is characterized by alterations on muscle fiber architecture, contractile protein integrity, and mitochondrial dysfunction. Exogenous and endogenous sources of reactive oxygen species (ROS) are present in COPD pathology. One of the endogenous sources of ROS is represented by mitochondria. Evidence demonstrated that vitamin D plays a crucial role for the maintenance of skeletal muscle health. Vitamin D deficiency affects oxidative stress and mitochondrial function influencing disease course through an effect on muscle function in COPD patients. This review will focus on vitamin-D-linked mechanisms that could modulate and ameliorate the damage response to free radicals in muscle fibers, evaluating vitamin D supplementation with enough potent effect to contrast mitochondrial impairment, but which avoids potential severe side effects.}, } @article {pmid35453370, year = {2022}, author = {Hambardikar, V and Guitart-Mampel, M and Scoma, ER and Urquiza, P and Nagana, GGA and Raftery, D and Collins, JA and Solesio, ME}, title = {Enzymatic Depletion of Mitochondrial Inorganic Polyphosphate (polyP) Increases the Generation of Reactive Oxygen Species (ROS) and the Activity of the Pentose Phosphate Pathway (PPP) in Mammalian Cells.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {35453370}, issn = {2076-3921}, support = {R00 AG055701/AG/NIA NIH HHS/United States ; }, abstract = {Inorganic polyphosphate (polyP) is an ancient biopolymer that is well preserved throughout evolution and present in all studied organisms. In mammals, it shows a high co-localization with mitochondria, and it has been demonstrated to be involved in the homeostasis of key processes within the organelle, including mitochondrial bioenergetics. However, the exact extent of the effects of polyP on the regulation of cellular bioenergetics, as well as the mechanisms explaining these effects, still remain poorly understood. Here, using HEK293 mammalian cells under Wild-type (Wt) and MitoPPX (cells enzymatically depleted of mitochondrial polyP) conditions, we show that depletion of polyP within mitochondria increased oxidative stress conditions. This is characterized by enhanced mitochondrial O2[-] and intracellular H2O2 levels, which may be a consequence of the dysregulation of oxidative phosphorylation (OXPHOS) that we have demonstrated in MitoPPX cells in our previous work. These findings were associated with an increase in basal peroxiredoxin-1 (Prx1), superoxide dismutase-2 (SOD2), and thioredoxin (Trx) antioxidant protein levels. Using [13]C-NMR and immunoblotting, we assayed the status of glycolysis and the pentose phosphate pathway (PPP) in Wt and MitoPPX cells. Our results show that MitoPPX cells display a significant increase in the activity of the PPP and an increase in the protein levels of transaldolase (TAL), which is a crucial component of the non-oxidative phase of the PPP and is involved in the regulation of oxidative stress. In addition, we observed a trend towards increased glycolysis in MitoPPX cells, which corroborates our prior work. Here, for the first time, we show the crucial role played by mitochondrial polyP in the regulation of mammalian redox homeostasis. Moreover, we demonstrate a significant effect of mitochondrial polyP on the regulation of global cellular bioenergetics in these cells.}, } @article {pmid35453058, year = {2022}, author = {Coleman, PS and Parlo, RA}, title = {Cancer's camouflage: Microvesicle shedding from cholesterol-rich tumor plasma membranes might blindfold first-responder immunosurveillance strategies.}, journal = {European journal of cell biology}, volume = {101}, number = {2}, pages = {151219}, doi = {10.1016/j.ejcb.2022.151219}, pmid = {35453058}, issn = {1618-1298}, mesh = {Animals ; Cell Membrane/metabolism ; Cholesterol/metabolism ; *Lipid Bilayers ; Mammals/metabolism ; Membrane Lipids/metabolism ; Monitoring, Immunologic ; *Neoplasms ; }, abstract = {Intermediary metabolism of tumors is characterized, in part, by a dysregulation of the cholesterol biosynthesis pathway at its rate-controlling enzyme providing the molecular basis for tumor membranes (mitochondria, plasma membrane) to become enriched with cholesterol (Bloch, 1965; Feo et al., 1975; Brown and Goldstein, 1980; Goldstein and Brown, 1990). Cholesterol enriched tumor mitochondria manifest preferential citrate export, thereby providing a continuous supply of substrate precursor for the tumor's dysregulated cholesterogenesis via a "truncated" Krebs/TCA cycle (Kaplan et al., 1986; Coleman et al., 1997). Proliferating tumors shed elevated amounts of plasma membrane-derived extracellular vesicles (pmEV) compared with normal tissues (van Blitterswijk et al., 1979; Black, 1980). Coordination of these metabolic phenomena in tumors supports the enhanced intercalation of cholesterol within the plasma membrane lipid bilayer's cytoplasmic face, the promotion of outward protrusions from the plasma membrane, and the evolution of cholesterol enriched pmEV. The pmEV shed by tumors possess elevated cholesterol and concentrated cell surface antigen clusters found on the tumor cells themselves (Kim et al., 2002). Upon exfoliation, saturation of the extracellular milieu with tumor-derived pmEV could allow early onset mammalian immune surveillance mechanisms to become "blind" to an evolving cancer and lose their ability to detect and initiate strategies to destroy the cancer. However, a molecular mechanism is lacking that would help explain how cholesterol enrichment of the pmEV inner lipid bilayer might allow the tumor cell to evade the host immune system. We offer a hypothesis, endorsed by published mathematical modeling of biomembrane structure as well as by decades of in vivo data with diverse cancers, that a cholesterol enriched inner bilayer leaflet, coupled with a logarithmic expansion in surface area of shed tumor pmEV load relative to its derivative cancer cell, conspire to force exposure of otherwise unfamiliar membrane integral protein domains as antigenic epitopes to the host's circulating immune surveillance system, allowing the tumor cells to evade destruction. We provide elementary numerical estimations comparing the amount of pmEV shed from tumor versus normal cells.}, } @article {pmid35452707, year = {2022}, author = {Chen, Q and Chen, L and Liao, CQ and Wang, X and Wang, M and Huang, GH}, title = {Comparative mitochondrial genome analysis and phylogenetic relationship among lepidopteran species.}, journal = {Gene}, volume = {830}, number = {}, pages = {146516}, doi = {10.1016/j.gene.2022.146516}, pmid = {35452707}, issn = {1879-0038}, mesh = {Animals ; *Butterflies/genetics ; *Genome, Mitochondrial ; *Lepidoptera/genetics ; Mitochondria/genetics ; *Moths/genetics ; Phylogeny ; RNA, Transfer/genetics ; }, abstract = {Lepidoptera has rich species including many agricultural pests and economical insects around the world. The mitochondrial genomes (mitogenomes) were utilized to explore the phylogenetic relationships between difference taxonomic levels in Lepidoptera. However, the knowledge of mitogenomic characteristics and phylogenetic position about superfamily-level in this order is unresolved. In this study, we integrated 794 mitogenomes consisting of 37 genes and a noncoding control region, which covered 26 lepidopteran superfamilies from newly sequenced and publicly available genomes for comparative genomic and phylogenetic analysis. In primitive taxon, putative start codon of cox1 gene was ATA or ATT instead of CGA, but stop codon of that showed four types, namely TAA, TAG, TA and T. The 7-bp overlap between atp8 and atp6 presented as "ATGATAA". Moreover, the most frequently utilized amino acids were leucine (UUA) in 13 PCGs. Phylogenetic analysis showed that the main backbone relationship in Lepidoptera was (Hepialoidea + (Nepticuloidea + (Adeloidea + (Tischerioidea + (Tineoidea + (Yponomeutoidea + (Gracillarioidea + (Papilionoidea + ((Zygaenoidea + Tortricoidea) + (Gelechioidea + (Pyraloidea + ((Geometroidea + Noctuoidea) + (Lasiocampoidea + Bombycoidea))))))))))))).}, } @article {pmid35451706, year = {2022}, author = {Vella, A and Vella, N and Acosta-Díaz, C}, title = {The first complete mitochondrial genomes for Serranus papilionaceus and Serranus scriba, and their phylogenetic position within Serranidae.}, journal = {Molecular biology reports}, volume = {49}, number = {7}, pages = {6295-6302}, pmid = {35451706}, issn = {1573-4978}, mesh = {Animals ; *Bass/genetics ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial/genetics ; Phylogeny ; RNA, Ribosomal/genetics ; }, abstract = {BACKGROUND: Butterfly-winged comber, Serranus papilionaceus Valenciennes, 1832, was recently resurrected and so it is no longer considered as a junior synonym of the Painted comber, Serranus scriba (Linneus, 1758). This calls for a more comprehensive phylogenetic assessment using mitochondria DNA genomes to better understand the relationship and delineate these two species.

METHODS AND RESULTS: Next-generation Sequencing was applied to sequence the genome of these two Serranus species. The data generated was then used to construct the mitochondrial genome of these two species. This produced the first complete mitochondrial genomes for the genus Serranus here represented by Serranus papilionaceus and Serranus scriba. These two mitochondrial genomes are 16,514 bp and 16,512 bp respectively, and both contained the typical 37 genes found in vertebrates (13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs), together with the OL and the control region.

CONCLUSIONS: These mitochondrial genomes provide a new insight into the phylogenetic and evolutionary connections between the various subfamilies within Serranidae, while providing new molecular data that can be applied to discriminate between the studied species.}, } @article {pmid35446942, year = {2022}, author = {Gil Del Alcazar, CR and Trinh, A and Alečković, M and Rojas Jimenez, E and Harper, NW and Oliphant, MUJ and Xie, S and Krop, ED and Lulseged, B and Murphy, KC and Keenan, TE and Van Allen, EM and Tolaney, SM and Freeman, GJ and Dillon, DA and Muthuswamy, SK and Polyak, K}, title = {Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer.}, journal = {Cancer immunology research}, volume = {10}, number = {6}, pages = {680-697}, pmid = {35446942}, issn = {2326-6074}, support = {R35 CA197623/CA/NCI NIH HHS/United States ; P50 CA168504/CA/NCI NIH HHS/United States ; T32 CA009172/CA/NCI NIH HHS/United States ; K00 CA223023/CA/NCI NIH HHS/United States ; R35 CA232128/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Breast Neoplasms/genetics/immunology/therapy ; Female ; Hormones ; Humans ; Immunologic Factors ; Immunotherapy ; Mice ; Rats ; Rats, Sprague-Dawley ; Receptors, Antigen, T-Cell ; }, abstract = {Animal models are critical for the preclinical validation of cancer immunotherapies. Unfortunately, mouse breast cancer models do not faithfully reproduce the molecular subtypes and immune environment of the human disease. In particular, there are no good murine models of estrogen receptor-positive (ER+) breast cancer, the predominant subtype in patients. Here, we show that Nitroso-N-methylurea-induced mammary tumors in outbred Sprague-Dawley rats recapitulate the heterogeneity for mutational profiles, ER expression, and immune evasive mechanisms observed in human breast cancer. We demonstrate the utility of this model for preclinical studies by dissecting mechanisms of response to immunotherapy using combination TGFBR inhibition and PD-L1 blockade. Short-term treatment of early-stage tumors induced durable responses. Gene expression profiling and spatial mapping classified tumors as inflammatory and noninflammatory, and identified IFNγ, T-cell receptor (TCR), and B-cell receptor (BCR) signaling, CD74/MHC II, and epithelium-interacting CD8+ T cells as markers of response, whereas the complement system, M2 macrophage phenotype, and translation in mitochondria were associated with resistance. We found that the expression of CD74 correlated with leukocyte fraction and TCR diversity in human breast cancer. We identified a subset of rat ER+ tumors marked by expression of antigen-processing genes that had an active immune environment and responded to treatment. A gene signature characteristic of these tumors predicted disease-free survival in patients with ER+ Luminal A breast cancer and overall survival in patients with metastatic breast cancer receiving anti-PD-L1 therapy. We demonstrate the usefulness of this preclinical model for immunotherapy and suggest examination to expand immunotherapy to a subset of patients with ER+ disease. See related Spotlight by Roussos Torres, p. 672.}, } @article {pmid35446419, year = {2022}, author = {Fields, PD and Waneka, G and Naish, M and Schatz, MC and Henderson, IR and Sloan, DB}, title = {Complete Sequence of a 641-kb Insertion of Mitochondrial DNA in the Arabidopsis thaliana Nuclear Genome.}, journal = {Genome biology and evolution}, volume = {14}, number = {5}, pages = {}, pmid = {35446419}, issn = {1759-6653}, support = {R01 GM118046/GM/NIGMS NIH HHS/United States ; BB/V003984/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Arabidopsis/genetics ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; In Situ Hybridization, Fluorescence ; Mitochondria/genetics ; Sequence Analysis, DNA ; }, abstract = {Intracellular transfers of mitochondrial DNA continue to shape nuclear genomes. Chromosome 2 of the model plant Arabidopsis thaliana contains one of the largest known nuclear insertions of mitochondrial DNA (numts). Estimated at over 600 kb in size, this numt is larger than the entire Arabidopsis mitochondrial genome. The primary Arabidopsis nuclear reference genome contains less than half of the numt because of its structural complexity and repetitiveness. Recent data sets generated with improved long-read sequencing technologies (PacBio HiFi) provide an opportunity to finally determine the accurate sequence and structure of this numt. We performed a de novo assembly using sequencing data from recent initiatives to span the Arabidopsis centromeres, producing a gap-free sequence of the Chromosome 2 numt, which is 641 kb in length and has 99.933% nucleotide sequence identity with the actual mitochondrial genome. The numt assembly is consistent with the repetitive structure previously predicted from fiber-based fluorescent in situ hybridization. Nanopore sequencing data indicate that the numt has high levels of cytosine methylation, helping to explain its biased spectrum of nucleotide sequence divergence and supporting previous inferences that it is transcriptionally inactive. The original numt insertion appears to have involved multiple mitochondrial DNA copies with alternative structures that subsequently underwent an additional duplication event within the nuclear genome. This work provides insights into numt evolution, addresses one of the last unresolved regions of the Arabidopsis reference genome, and represents a resource for distinguishing between highly similar numt and mitochondrial sequences in studies of transcription, epigenetic modifications, and de novo mutations.}, } @article {pmid35444563, year = {2022}, author = {Mendez-Romero, O and Ricardez-García, C and Castañeda-Tamez, P and Chiquete-Félix, N and Uribe-Carvajal, S}, title = {Thriving in Oxygen While Preventing ROS Overproduction: No Two Systems Are Created Equal.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {874321}, pmid = {35444563}, issn = {1664-042X}, abstract = {From 2.5 to 2.0 billion years ago, atmospheric oxygen concentration [O2] rose thousands of times, leading to the first mass extinction. Reactive Oxygen Species (ROS) produced by the non-catalyzed partial reduction of O2 were highly toxic eliminating many species. Survivors developed different strategies to cope with ROS toxicity. At the same time, using O2 as the final acceptor in respiratory chains increased ATP production manifold. Thus, both O2 and ROS were strong drivers of evolution, as species optimized aerobic metabolism while developing ROS-neutralizing mechanisms. The first line of defense is preventing ROS overproduction and two mechanisms were developed in parallel: 1) Physiological uncoupling systems (PUS), which increase the rate of electron fluxes in respiratory systems. 2) Avoidance of excess [O2]. However, it seems that as avoidance efficiency improved, PUSs became less efficient. PUS includes branched respiratory chains and proton sinks, which may be proton specific, the mitochondrial uncoupling proteins (UCPs) or unspecific, the mitochondrial permeability transition pore (PTP). High [O2] avoidance also involved different strategies: 1) Cell association, as in biofilms or in multi-cellularity allowed gas-permeable organisms (oxyconformers) from bacterial to arthropods to exclude O2. 2) Motility, to migrate from hypoxic niches. 3) Oxyregulator organisms: as early as in fish, and O2-impermeable epithelium excluded all gases and only exact amounts entered through specialized respiratory systems. Here we follow the parallel evolution of PUS and O2-avoidance, PUS became less critical and lost efficiency. In regard, to proton sinks, there is fewer evidence on their evolution, although UCPs have indeed drifted in function while in some species it is not clear whether PTPs exist.}, } @article {pmid35441886, year = {2022}, author = {Egusquiza-Alvarez, CA and Robles-Flores, M}, title = {An approach to p32/gC1qR/HABP1: a multifunctional protein with an essential role in cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {148}, number = {8}, pages = {1831-1854}, pmid = {35441886}, issn = {1432-1335}, mesh = {Carrier Proteins ; Humans ; Ligands ; Mitochondria/metabolism ; *Mitochondrial Proteins/metabolism ; *Neoplasms/pathology ; }, abstract = {P32/gC1qR/HABP1 is a doughnut-shaped acidic protein, highly conserved in eukaryote evolution and ubiquitous in the organism. Although its canonical subcellular localization is the mitochondria, p32 can also be found in the cytosol, nucleus, cytoplasmic membrane, and it can be secreted. Therefore, it is considered a multicompartmental protein. P32 can interact with many physiologically divergent ligands in each subcellular location and modulate their functions. The main ligands are C1q, hyaluronic acid, calreticulin, CD44, integrins, PKC, splicing factor ASF/SF2, and several microbial proteins. Among the functions in which p32 participates are mitochondrial metabolism and dynamics, apoptosis, splicing, immune response, inflammation, and modulates several cell signaling pathways. Notably, p32 is overexpressed in a significant number of epithelial tumors, where its expression level negatively correlates with patient survival. Several studies of gain and/or loss of function in cancer cells have demonstrated that p32 is a promoter of malignant hallmarks such as proliferation, cell survival, chemoresistance, angiogenesis, immunoregulation, migration, invasion, and metastasis. All of this strongly suggests that p32 is a potential diagnostic molecule and therapeutic target in cancer. Indeed, preclinical advances have been made in developing therapeutic strategies using p32 as a target. They include tumor homing peptides, monoclonal antibodies, an intracellular inhibitor, a p32 peptide vaccine, and p32 CAR T cells. These advances are promising and will allow soon to include p32 as part of targeted cancer therapies.}, } @article {pmid35435757, year = {2022}, author = {Nakabachi, A and Moran, NA}, title = {Extreme Polyploidy of Carsonella, an Organelle-Like Bacterium with a Drastically Reduced Genome.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0035022}, pmid = {35435757}, issn = {2165-0497}, mesh = {Animals ; Bacteria/genetics ; *Gammaproteobacteria ; Genome, Bacterial ; *Hemiptera/genetics/microbiology ; Organelles ; Phylogeny ; Polyploidy ; Symbiosis ; }, abstract = {Polyploidy is the state of having multiple copies of the genome within a nucleus or a cell, which has repeatedly evolved across the domains of life. Whereas most bacteria are monoploid, some bacterial species and endosymbiotic organelles that are derived from bacteria are stably polyploid. In the present study, using absolute quantitative PCR, we assessed the ploidy of Candidatus Carsonella ruddii (Gammaproteobacteria, Oceanospirillales), the obligate symbiont of the hackberry petiole gall psyllid, Pachypsylla venusta (Hemiptera, Psylloidea). The genome of this symbiont is one of the smallest known for cellular organisms, at 160 kb. The analysis revealed that Carsonella within a single bacteriocyte has ∼6 × 10[4] copies of the genome, indicating that some Carsonella cells can contain thousands or even tens of thousands of genomic copies per cell. The basis of polyploidy of Carsonella is unknown, but it potentially plays a role in the repair of DNA damage through homologous recombination. IMPORTANCE Mitochondria and plastids are endosymbiotic organelles in eukaryotic cells and are derived from free-living bacteria. They have many highly reduced genomes from which numerous genes have been transferred to the host nucleus. Similar, but more recently established, symbiotic systems are observed in some insect lineages. Although the genomic sequence data of such bacterial symbionts are rapidly accumulating, little is known about their ploidy. The present study revealed that a bacterium with a drastically reduced genome is an extreme polyploid, which is reminiscent of the case of organelles.}, } @article {pmid35418016, year = {2022}, author = {Yuan, F and Lan, X}, title = {Sequencing the organelle genomes of Bougainvillea spectabilis and Mirabilis jalapa (Nyctaginaceae).}, journal = {BMC genomic data}, volume = {23}, number = {1}, pages = {28}, pmid = {35418016}, issn = {2730-6844}, mesh = {*Genome, Chloroplast/genetics ; *Genome, Mitochondrial/genetics ; *Mirabilis/genetics ; Mitochondria/genetics ; *Nyctaginaceae/genetics ; }, abstract = {OBJECTIVES: Mirabilis jalapa L. and Bougainvillea spectabilis are two Mirabilis species known for their ornamental and pharmaceutical values. The organelle genomes are highly conserved with a rapid evolution rate making them suitable for evolutionary studies. Therefore, mitochondrial and chloroplast genomes of B. spectabilis and M. jalapa were sequenced to understand their evolutionary relationship with other angiosperms.

DATA DESCRIPTION: Here, we report the complete mitochondrial genomes of B. spectabilis and M. jalapa (343,746 bp and 267,334 bp, respectively) and chloroplast genomes of B. spectabilis (154,520 bp) and M. jalapa (154,532 bp) obtained from Illumina NovaSeq. The mitochondrial genomes of B. spectabilis and M. jalapa consisted of 70 and 72 genes, respectively. Likewise, the chloroplast genomes of B. spectabilis and M. jalapa contained 131 and 132 genes, respectively. The generated genomic data will be useful for molecular characterization and evolutionary studies.}, } @article {pmid35409414, year = {2022}, author = {Tsai, HC and Hsieh, CH and Hsu, CW and Hsu, YH and Chien, LF}, title = {Cloning and Organelle Expression of Bamboo Mitochondrial Complex I Subunits Nad1, Nad2, Nad4, and Nad5 in the Yeast Saccharomyces cerevisiae.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409414}, issn = {1422-0067}, mesh = {Cloning, Molecular ; DNA, Mitochondrial/genetics ; *Electron Transport Complex I/genetics ; Mitochondria/genetics ; Phylogeny ; *Saccharomyces cerevisiae/genetics ; }, abstract = {Mitochondrial respiratory complex I catalyzes electron transfer from NADH to ubiquinone and pumps protons from the matrix into the intermembrane space. In particular, the complex I subunits Nad1, Nad2, Nad4, and Nad5, which are encoded by the nad1, nad2, nad4, and nad5 genes, reside at the mitochondrial inner membrane and possibly function as proton (H[+]) and ion translocators. To understand the individual functional roles of the Nad1, Nad2, Nad4, and Nad5 subunits in bamboo, each cDNA of these four genes was cloned into the pYES2 vector and expressed in the mitochondria of the yeast Saccharomyces cerevisiae. The mitochondrial targeting peptide mt gene (encoding MT) and the egfp marker gene (encoding enhanced green fluorescent protein, EGFP) were fused at the 5'-terminal and 3'-terminal ends, respectively. The constructed plasmids were then transformed into yeast. RNA transcripts and fusion protein expression were observed in the yeast transformants. Mitochondrial localizations of the MT-Nad1-EGFP, MT-Nad2-EGFP, MT-Nad4-EGFP, and MT-Nad5-EGFP fusion proteins were confirmed by fluorescence microscopy. The ectopically expressed bamboo subunits Nad1, Nad2, Nad4, and Nad5 may function in ion translocation, which was confirmed by growth phenotype assays with the addition of different concentrations of K[+], Na[+], or H[+].}, } @article {pmid35409376, year = {2022}, author = {Kasperski, A}, title = {Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409376}, issn = {1422-0067}, mesh = {Cell Physiological Phenomena ; Cell Transformation, Neoplastic/metabolism ; *Energy Metabolism ; Humans ; Mitochondria/metabolism ; *Neoplasms/metabolism ; }, abstract = {In view of unified cell bioenergetics, cell bioenergetic problems related to cell overenergization can cause excessive disturbances in current cell fate and, as a result, lead to a change of cell-fate. At the onset of the problem, cell overenergization of multicellular organisms (especially overenergization of mitochondria) is solved inter alia by activation and then stimulation of the reversible Crabtree effect by cells. Unfortunately, this apparently good solution can also lead to a much bigger problem when, despite the activation of the Crabtree effect, cell overenergization persists for a long time. In such a case, cancer transformation, along with the Warburg effect, may occur to further reduce or stop the charging of mitochondria by high-energy molecules. Understanding the phenomena of cancer transformation and cancer development has become a real challenge for humanity. To date, many models have been developed to understand cancer-related mechanisms. Nowadays, combining all these models into one coherent universal model of cancer transformation and development can be considered a new challenge. In this light, the aim of this article is to present such a potentially universal model supported by a proposed new model of cellular functionality evolution. The methods of fighting cancer resulting from unified cell bioenergetics and the two presented models are also considered.}, } @article {pmid35408834, year = {2022}, author = {Scaltsoyiannes, V and Corre, N and Waltz, F and Giegé, P}, title = {Types and Functions of Mitoribosome-Specific Ribosomal Proteins across Eukaryotes.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35408834}, issn = {1422-0067}, mesh = {Cryoelectron Microscopy ; Eukaryota/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; *Mitochondrial Ribosomes/metabolism ; RNA, Ribosomal/metabolism ; *Ribosomal Proteins/metabolism ; }, abstract = {Mitochondria are key organelles that combine features inherited from their bacterial endosymbiotic ancestor with traits that arose during eukaryote evolution. These energy producing organelles have retained a genome and fully functional gene expression machineries including specific ribosomes. Recent advances in cryo-electron microscopy have enabled the characterization of a fast-growing number of the low abundant membrane-bound mitochondrial ribosomes. Surprisingly, mitoribosomes were found to be extremely diverse both in terms of structure and composition. Still, all of them drastically increased their number of ribosomal proteins. Interestingly, among the more than 130 novel ribosomal proteins identified to date in mitochondria, most of them are composed of a-helices. Many of them belong to the nuclear encoded super family of helical repeat proteins. Here we review the diversity of functions and the mode of action held by the novel mitoribosome proteins and discuss why these proteins that share similar helical folds were independently recruited by mitoribosomes during evolution in independent eukaryote clades.}, } @article {pmid35406135, year = {2022}, author = {Snell, TW and Carberry, J}, title = {Astaxanthin Bioactivity Is Determined by Stereoisomer Composition and Extraction Method.}, journal = {Nutrients}, volume = {14}, number = {7}, pages = {}, pmid = {35406135}, issn = {2072-6643}, mesh = {Animals ; *Antioxidants/pharmacology ; Reactive Oxygen Species/metabolism ; Stereoisomerism ; *Xanthophylls/chemistry/pharmacology ; }, abstract = {Astaxanthin (ASX) is a natural product and one of the most powerful antioxidants known. It has significant effects on the metabolism of many animals, increasing fecundity, egg yolk volume, growth rates, immune responses, and disease resistance. A large part of the bioactivity of ASX is due to its targeting of mitochondria, where it inserts itself into cell membranes. Here, ASX stabilizes membranes and acts as a powerful antioxidant, protecting mitochondria from damage by reactive oxygen species (ROS). ROS are ubiquitous by-products of energy metabolism that must be tightly regulated by cells, lest they bind to and inactivate proteins, DNA and RNA, lipids, and signaling molecules. Most animals cannot synthesize ASX, so they need to acquire it in their diet. ASX is easily thermally denatured during extraction, and its high hydrophobicity limits its bioavailability. Our focus in this review is to contrast the bioactivity of different ASX stereoisomers and how extraction methods can denature ASX, compromising its bioavailability and bioactivity. We discuss the commercial sources of astaxanthin, structure of stereoisomers, relative bioavailability and bioactivity of ASX stereoisomers, mechanisms of ASX bioactivity, evolution of carotenoids, and why mitochondrial targeting makes ASX such an effective antioxidant.}, } @article {pmid35397926, year = {2022}, author = {Zhu, D and Li, X and Tian, Y}, title = {Mitochondrial-to-nuclear communication in aging: an epigenetic perspective.}, journal = {Trends in biochemical sciences}, volume = {47}, number = {8}, pages = {645-659}, doi = {10.1016/j.tibs.2022.03.008}, pmid = {35397926}, issn = {0968-0004}, mesh = {Cell Nucleus/metabolism ; Epigenesis, Genetic ; *Longevity/physiology ; *Mitochondria/metabolism ; }, abstract = {Age-associated changes in mitochondria are closely involved in aging. Apart from the established roles in bioenergetics and biosynthesis, mitochondria are signaling organelles that communicate their fitness to the nucleus, triggering transcriptional programs to adapt homeostasis stress that is essential for organismal health and aging. Emerging studies revealed that mitochondrial-to-nuclear (mito-nuclear) communication via altered levels of mitochondrial metabolites or stress signals causes various epigenetic changes, facilitating efforts to maintain homeostasis and affect aging. Here, we summarize recent studies on the mechanisms by which mito-nuclear communication modulates epigenomes and their effects on regulating the aging process. Insights into understanding how mitochondrial metabolites serve as prolongevity signals and how aging affects this communication will help us develop interventions to promote longevity and health.}, } @article {pmid35391231, year = {2022}, author = {Chen, Z and Liu, F and Li, D and Xu, X}, title = {Four new species of the primitively segmented spider genus Songthela (Mesothelae, Liphistiidae) from Chongqing Municipality, China.}, journal = {Zootaxa}, volume = {5091}, number = {4}, pages = {546-558}, doi = {10.11646/zootaxa.5091.4.2}, pmid = {35391231}, issn = {1175-5334}, mesh = {Animals ; China ; DNA Barcoding, Taxonomic ; DNA, Mitochondrial/genetics ; Female ; Male ; Mitochondria/genetics ; *Spiders/genetics ; }, abstract = {This paper reports four new species of the primitively segmented spider genus Songthela from Chongqing Municipality, China, based on morphological characters of both males and females: S. jinyun sp. nov., S. longbao sp. nov., S. serriformis sp. nov. and S. wangerbao sp. nov. We also provide the GenBank accession codes of mitochondrial DNA barcode gene, cytochrome c oxidase subunit I (COI), for the holotype of four new species for future identification.}, } @article {pmid35391113, year = {2022}, author = {Lobon-Rovira, J and Conradie, W and Pinto, PV and Keates, C and Edwards, S and Plessis, AD and Branch, WR}, title = {Systematic revision of Afrogecko ansorgii (Boulenger, 1907) (Sauria: Gekkonidae) from western Angola.}, journal = {Zootaxa}, volume = {5124}, number = {4}, pages = {401-430}, doi = {10.11646/zootaxa.5124.4.1}, pmid = {35391113}, issn = {1175-5334}, mesh = {Angola ; Animals ; Cell Nucleus/genetics ; *Lizards/genetics ; Male ; Mitochondria ; Phylogeny ; }, abstract = {Here we provide the first phylogenetic analysis that include Afrogecko ansorgii and a detailed morphological comparison with other species of leaf-toed geckos. For this purpose, we used two mitochondrial (16S, ND2) and four nuclear (RAG1, RAG2, CMOS, PDC) genes to produce a robust phylogenetic reconstruction. This allowed us to show that A. ansorgii is not related as previously believed to circum-Indian Ocean leaf-toed geckos and is rather more closely related to other Malagasy leaf-toed geckos. Additionally, we explore and compare osteological variation in A. ansorgii skulls through High Resolution X-ray Computed Tomography with previously published material. This allowed us to describe herein a new genus, Bauerius gen. nov., and additionally provide a detailed redescription of the species (including the first description of male material), supplementing the limited original description and type series, which consisted of only two females.}, } @article {pmid35390830, year = {2021}, author = {Takano, KT and Gao, JJ and Hu, YG and Li, NN and Yafuso, M and Suwito, A and Repin, R and Pungga, RAS and Meleng, PA and Kaliang, CH and Chong, L and Toda, MJ}, title = {Phylogeny, taxonomy and flower-breeding ecology of the Colocasiomyia cristata species group (Diptera: Drosophilidae), with descriptions of ten new species.}, journal = {Zootaxa}, volume = {5079}, number = {1}, pages = {170}, doi = {10.11646/zootaxa.5079.1.1}, pmid = {35390830}, issn = {1175-5334}, mesh = {Animals ; *Diptera ; *Drosophilidae ; Flowers ; Mitochondria ; Phylogeny ; Plant Breeding ; }, abstract = {The phylogeny of the Colocasiomyia cristata species group is reconstructed as a hypothesis, based on DNA sequences of two mitochondrial and six nuclear genes and 51 morphological characters. The resulting tree splits this species group into two clades, one of which corresponds to the colocasiae subgroup. Therefore, a new species subgroup named as the cristata subgroup is established for the other clade. Within the cristata subgroup, three subclades are recognized and each of them is defined as a species complex: the cristata complex composed of five species (including three new ones: C. kinabaluana sp. nov., C. kotana sp. nov. and C. matthewsi sp. nov.), the sabahana complex of two species (C. sabahana sp. nov. and C. sarawakana sp. nov.), and the xenalocasiae complex of five species (including C. sumatrana sp. nov. and C. leucocasiae sp. nov.). There are, however, three new species (C. ecornuta sp. nov., C. grandis sp. nov. and C. vieti sp. nov.) not assigned to any species complex. In addition, breeding habits are described for four cristata-subgroup species, each of which monopolizes its specific host plant. And, data of host-plant use are compiled for all species of the cristata group from records at various localities in the Oriental and Papuan regions. The evolution of host-plant selection and sharing modes is considered by mapping host-plant genera of each species on the phylogenetic tree resulting from the present study.}, } @article {pmid35390639, year = {2022}, author = {Schneider, A}, title = {Evolution and diversification of mitochondrial protein import systems.}, journal = {Current opinion in cell biology}, volume = {75}, number = {}, pages = {102077}, doi = {10.1016/j.ceb.2022.102077}, pmid = {35390639}, issn = {1879-0410}, mesh = {Animals ; Carrier Proteins/metabolism ; Mammals/metabolism ; Membrane Proteins/metabolism ; Mitochondria/metabolism ; *Mitochondrial Membranes/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; Protein Transport/physiology ; Saccharomyces cerevisiae/metabolism ; }, abstract = {More than 95% of mitochondrial proteins are encoded in the nucleus, synthesised in the cytosol and imported into the organelle. The evolution of mitochondrial protein import systems was therefore a prerequisite for the conversion of the α-proteobacterial mitochondrial ancestor into an organelle. Here, I review that the origin of the mitochondrial outer membrane import receptors can best be understood by convergent evolution. Subsequently, I discuss an evolutionary scenario that was proposed to explain the diversification of the inner membrane carrier protein translocases between yeast and mammals. Finally, I illustrate a scenario that can explain how the two specialised inner membrane protein translocase complexes found in most eukaryotes were reduced to a single multifunctional one in trypanosomes.}, } @article {pmid35383845, year = {2022}, author = {Sharbrough, J and Conover, JL and Fernandes Gyorfy, M and Grover, CE and Miller, ER and Wendel, JF and Sloan, DB}, title = {Global Patterns of Subgenome Evolution in Organelle-Targeted Genes of Six Allotetraploid Angiosperms.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35383845}, issn = {1537-1719}, mesh = {Cell Nucleus/genetics ; Evolution, Molecular ; Genome, Plant ; *Magnoliopsida/genetics ; Plastids/genetics ; Polyploidy ; Ribulose-Bisphosphate Carboxylase/genetics ; }, abstract = {Whole-genome duplications (WGDs) are a prominent process of diversification in eukaryotes. The genetic and evolutionary forces that WGD imposes on cytoplasmic genomes are not well understood, despite the central role that cytonuclear interactions play in eukaryotic function and fitness. Cellular respiration and photosynthesis depend on successful interaction between the 3,000+ nuclear-encoded proteins destined for the mitochondria or plastids and the gene products of cytoplasmic genomes in multi-subunit complexes such as OXPHOS, organellar ribosomes, Photosystems I and II, and Rubisco. Allopolyploids are thus faced with the critical task of coordinating interactions between the nuclear and cytoplasmic genes that were inherited from different species. Because the cytoplasmic genomes share a more recent history of common descent with the maternal nuclear subgenome than the paternal subgenome, evolutionary "mismatches" between the paternal subgenome and the cytoplasmic genomes in allopolyploids might lead to the accelerated rates of evolution in the paternal homoeologs of allopolyploids, either through relaxed purifying selection or strong directional selection to rectify these mismatches. We report evidence from six independently formed allotetraploids that the subgenomes exhibit unequal rates of protein-sequence evolution, but we found no evidence that cytonuclear incompatibilities result in altered evolutionary trajectories of the paternal homoeologs of organelle-targeted genes. The analyses of gene content revealed mixed evidence for whether the organelle-targeted genes are lost more rapidly than the non-organelle-targeted genes. Together, these global analyses provide insights into the complex evolutionary dynamics of allopolyploids, showing that the allopolyploid subgenomes have separate evolutionary trajectories despite sharing the same nucleus, generation time, and ecological context.}, } @article {pmid35379961, year = {2022}, author = {Mok, BY and Kotrys, AV and Raguram, A and Huang, TP and Mootha, VK and Liu, DR}, title = {CRISPR-free base editors with enhanced activity and expanded targeting scope in mitochondrial and nuclear DNA.}, journal = {Nature biotechnology}, volume = {40}, number = {9}, pages = {1378-1387}, pmid = {35379961}, issn = {1546-1696}, support = {RM1 HG009490/HG/NHGRI NIH HHS/United States ; R35 GM118062/GM/NIGMS NIH HHS/United States ; R01 EB027793/EB/NIBIB NIH HHS/United States ; R35 GM122455/GM/NIGMS NIH HHS/United States ; T32 GM095450/GM/NIGMS NIH HHS/United States ; U01 AI142756/AI/NIAID NIH HHS/United States ; R01 EB031172/EB/NIBIB NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*CRISPR-Cas Systems ; Cytidine Deaminase/genetics ; DNA, Mitochondrial/genetics ; *Gene Editing ; Humans ; Mitochondria/genetics/metabolism ; }, abstract = {The all-protein cytosine base editor DdCBE uses TALE proteins and a double-stranded DNA-specific cytidine deaminase (DddA) to mediate targeted C•G-to-T•A editing. To improve editing efficiency and overcome the strict TC sequence-context constraint of DddA, we used phage-assisted non-continuous and continuous evolution to evolve DddA variants with improved activity and expanded targeting scope. Compared to canonical DdCBEs, base editors with evolved DddA6 improved mitochondrial DNA (mtDNA) editing efficiencies at TC by 3.3-fold on average. DdCBEs containing evolved DddA11 offered a broadened HC (H = A, C or T) sequence compatibility for both mitochondrial and nuclear base editing, increasing average editing efficiencies at AC and CC targets from less than 10% for canonical DdCBE to 15-30% and up to 50% in cell populations sorted to express both halves of DdCBE. We used these evolved DdCBEs to efficiently install disease-associated mtDNA mutations in human cells at non-TC target sites. DddA6 and DddA11 substantially increase the effectiveness and applicability of all-protein base editing.}, } @article {pmid35377454, year = {2022}, author = {Monteiro, LB and Prodonoff, JS and Favero de Aguiar, C and Correa-da-Silva, F and Castoldi, A and Bakker, NVT and Davanzo, GG and Castelucci, B and Pereira, JADS and Curtis, J and Büscher, J and Reis, LMD and Castro, G and Ribeiro, G and Virgílio-da-Silva, JV and Adamoski, D and Dias, SMG and Consonni, SR and Donato, J and Pearce, EJ and Câmara, NOS and Moraes-Vieira, PM}, title = {Leptin Signaling Suppression in Macrophages Improves Immunometabolic Outcomes in Obesity.}, journal = {Diabetes}, volume = {71}, number = {7}, pages = {1546-1561}, doi = {10.2337/db21-0842}, pmid = {35377454}, issn = {1939-327X}, mesh = {Adipose Tissue/metabolism ; Animals ; Inflammation/metabolism ; *Insulin Resistance ; *Leptin/metabolism ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL ; Obesity/metabolism ; }, abstract = {Obesity is a major concern for global health care systems. Systemic low-grade inflammation in obesity is a major risk factor for insulin resistance. Leptin is an adipokine secreted by the adipose tissue that functions by controlling food intake, leading to satiety. Leptin levels are increased in obesity. Here, we show that leptin enhances the effects of LPS in macrophages, intensifying the production of cytokines, glycolytic rates, and morphological and functional changes in the mitochondria through an mTORC2-dependent, mTORC1-independent mechanism. Leptin also boosts the effects of IL-4 in macrophages, leading to increased oxygen consumption, expression of macrophage markers associated with a tissue repair phenotype, and wound healing. In vivo, hyperleptinemia caused by diet-induced obesity increases the inflammatory response by macrophages. Deletion of leptin receptor and subsequently of leptin signaling in myeloid cells (ObR-/-) is sufficient to improve insulin resistance in obese mice and decrease systemic inflammation. Our results indicate that leptin acts as a systemic nutritional checkpoint to regulate macrophage fitness and contributes to obesity-induced inflammation and insulin resistance. Thus, specific interventions aimed at downstream modulators of leptin signaling may represent new therapeutic targets to treat obesity-induced systemic inflammation.}, } @article {pmid35360860, year = {2022}, author = {Bever, BW and Dietz, ZP and Sullins, JA and Montoya, AM and Bergthorsson, U and Katju, V and Estes, S}, title = {Mitonuclear Mismatch is Associated With Increased Male Frequency, Outcrossing, and Male Sperm Size in Experimentally-Evolved C. elegans.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {742272}, pmid = {35360860}, issn = {1664-8021}, abstract = {We provide a partial test of the mitonuclear sex hypothesis with the first controlled study of how male frequencies and rates of outcrossing evolve in response to mitonuclear mismatch by allowing replicate lineages of C. elegans nematodes containing either mitochondrial or nuclear mutations of electron transport chain (ETC) genes to evolve under three sexual systems: facultatively outcrossing (wildtype), obligately selfing, and obligately outcrossing. Among facultatively outcrossing lines, we found evolution of increased male frequency in at least one replicate line of all four ETC mutant backgrounds tested-nuclear isp-1, mitochondrial cox-1 and ctb-1, and an isp-1 IV; ctb-1M mitonuclear double mutant-and confirmed for a single line set (cox-1) that increased male frequency also resulted in successful outcrossing. We previously found the same result for lines evolved from another nuclear ETC mutant, gas-1. For several lines in the current experiment, however, male frequency declined to wildtype levels (near 0%) in later generations. Male frequency did not change in lines evolved from a wildtype control strain. Additional phenotypic assays of lines evolved from the mitochondrial cox-1 mutant indicated that evolution of high male frequency was accompanied by evolution of increased male sperm size and mating success with tester females, but that it did not translate into increased mating success with coevolved hermaphrodites. Rather, hermaphrodites' self-crossed reproductive fitness increased, consistent with sexually antagonistic coevolution. In accordance with evolutionary theory, males and sexual outcrossing may be most beneficial to populations evolving from a state of low ancestral fitness (gas-1, as previously reported) and less beneficial or deleterious to those evolving from a state of higher ancestral fitness (cox-1). In support of this idea, the obligately outcrossing fog-2 V; cox-1 M lines exhibited no fitness evolution compared to their ancestor, while facultatively outcrossing lines showed slight upward evolution of fitness, and all but one of the obligately selfing xol-1 X; cox-1 M lines evolved substantially increased fitness-even beyond wildtype levels. This work provides a foundation to directly test the effect of reproductive mode on the evolutionary dynamics of mitonuclear genomes, as well as whether compensatory mutations (nuclear or mitochondrial) can rescue populations from mitochondrial dysfunction.}, } @article {pmid35359176, year = {2022}, author = {Ceriotti, LF and Gatica-Soria, L and Sanchez-Puerta, MV}, title = {Cytonuclear coevolution in a holoparasitic plant with highly disparate organellar genomes.}, journal = {Plant molecular biology}, volume = {109}, number = {6}, pages = {673-688}, pmid = {35359176}, issn = {1573-5028}, mesh = {*Balanophoraceae/genetics ; Cell Nucleus/genetics ; Chloroplast Proteins/genetics ; Evolution, Molecular ; Gene Transfer, Horizontal ; Genome, Plant/genetics ; Phylogeny ; Plants/genetics ; *Plastids/genetics ; }, abstract = {Contrasting substitution rates in the organellar genomes of Lophophytum agree with the DNA repair, replication, and recombination gene content. Plastid and nuclear genes whose products form multisubunit complexes co-evolve. The organellar genomes of the holoparasitic plant Lophophytum (Balanophoraceae) show disparate evolution. In the plastid, the genome has been severely reduced and presents a > 85% AT content, while in the mitochondria most protein-coding genes have been replaced by homologs acquired by horizontal gene transfer (HGT) from their hosts (Fabaceae). Both genomes carry genes whose products form multisubunit complexes with those of nuclear genes, creating a possible hotspot of cytonuclear coevolution. In this study, we assessed the evolutionary rates of plastid, mitochondrial and nuclear genes, and their impact on cytonuclear evolution of genes involved in multisubunit complexes related to lipid biosynthesis and proteolysis in the plastid and those in charge of the oxidative phosphorylation in the mitochondria. Genes from the plastid and the mitochondria (both native and foreign) of Lophophytum showed extremely high and ordinary substitution rates, respectively. These results agree with the biased loss of plastid-targeted proteins involved in angiosperm organellar repair, replication, and recombination machinery. Consistent with the high rate of evolution of plastid genes, nuclear-encoded subunits of plastid complexes showed disproportionate increases in non-synonymous substitution rates, while those of the mitochondrial complexes did not show different rates than the control (i.e. non-organellar nuclear genes). Moreover, the increases in the nuclear-encoded subunits of plastid complexes were positively correlated with the level of physical interaction they possess with the plastid-encoded ones. Overall, these results suggest that a structurally-mediated compensatory factor may be driving plastid-nuclear coevolution in Lophophytum, and that mito-nuclear coevolution was not altered by HGT.}, } @article {pmid35358979, year = {2022}, author = {Risser, C and Tran Ba Loc, P and Binder-Foucard, F and Fabacher, T and Lefèvre, H and Sauvage, C and Sauleau, EA and Wolff, V}, title = {COVID-19 Impact on Stroke Admissions during France's First Epidemic Peak: An Exhaustive, Nationwide, Observational Study.}, journal = {Cerebrovascular diseases (Basel, Switzerland)}, volume = {51}, number = {5}, pages = {663-669}, pmid = {35358979}, issn = {1421-9786}, mesh = {Bayes Theorem ; *COVID-19/epidemiology ; Cohort Studies ; Communicable Disease Control ; Hospitalization ; Humans ; Pandemics ; *Stroke/diagnosis/epidemiology/therapy ; }, abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic continues to have great impacts on the care of non-COVID-19 patients. This was especially true during the first epidemic peak in France, which coincided with the national lockdown. The aim of this study was to identify whether a decrease in stroke admissions occurred in spring 2020, by analyzing the evolution of all stroke admissions in France from January 2019 to June 2020.

METHODS: We conducted a nationwide cohort study using the French national database of hospital admissions (Information Systems Medicalization Program) to extract exhaustive data on all hospitalizations in France with at least one stroke diagnosis between January 1, 2019, and June 30, 2020. The primary endpoint was the difference in the slope gradients of stroke hospitalizations between pre-epidemic, epidemic peak, and post-epidemic peak phases. Modeling was carried out using Bayesian techniques.

RESULTS: Stroke hospitalizations dropped from March 10, 2020 (slope gradient: -11.70), and began to rise again from March 22 (slope gradient: 2.090) to May 7. In total, there were 23,873 stroke admissions during the period March-April 2020, compared to 29,263 at the same period in 2019, representing a decrease of 18.42%. The percentage change was -15.63%, -25.19%, -18.62% for ischemic strokes, transient ischemic attacks, and hemorrhagic strokes, respectively.

DISCUSSION/CONCLUSION: Stroke hospitalizations in France experienced a decline during the first lockdown period, which cannot be explained by a sudden change in stroke incidence. This decline is therefore likely to be a direct, or indirect, result of the COVID-19 pandemic.}, } @article {pmid35353639, year = {2022}, author = {Lipko, NB}, title = {Photobiomodulation: Evolution and Adaptation.}, journal = {Photobiomodulation, photomedicine, and laser surgery}, volume = {40}, number = {4}, pages = {213-233}, doi = {10.1089/photob.2021.0145}, pmid = {35353639}, issn = {2578-5478}, mesh = {Humans ; Lasers ; *Low-Level Light Therapy/methods ; Mitochondria ; }, abstract = {Photobiomodulation (PBM) can be described as the intentional use of low-power laser or light-emitting diode light in the visible and near-infrared light spectra as a medical treatment to living biological tissues. This article describes the evolution of photochemical reactions on Earth, the mitochondria, and their implications in PBM; the science of light and energy (necessary to understand the mechanisms of PBM); and the clinical science of light as therapeutic medicine. Finally, selected reviews of current treatment protocols and ongoing research regarding the possibilities for the use of PBM in the human body are examined.}, } @article {pmid35351912, year = {2022}, author = {Lessios, HA and Hendler, G}, title = {Mitochondrial phylogeny of the brittle star genus Ophioderma.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {5304}, pmid = {35351912}, issn = {2045-2322}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Echinodermata/genetics ; *Evolution, Molecular ; Mitochondria/genetics ; Phylogeny ; }, abstract = {We reconstructed the mitochondrial phylogeny of the species of the brittle star genus Ophioderma, using sequences of the Cytochrome Oxidase I gene (COI) to address four questions: (i) Are the species of Ophioderma described on morphological evidence reflected in mitochondrial genealogy? (ii) Which species separated from which? (iii) When did speciation events occur? (iv) What is the rate of COI evolution in ophiuroids? We found that most of the 22 described species we sampled coincide with monophyletic clusters of COI sequences, but there are exceptions, most notably in the eastern Pacific, in which three undescribed species were indicated. The COI phylogeny lacks resolution in the deeper nodes, but it does show that there are four species pairs, the members of which are found on either side of the central American Isthmus. Two pairs with a genetic distance of ~ 4% between Atlantic and Pacific members were probably split during the final stages of Isthmus completion roughly 3 million years ago. The rate of divergence provided by these pairs allowed the calibration of a relaxed molecular clock. Estimated dates of divergence indicate that the lineages leading to extant species coalesce at times much older than congeneric species in other classes of echinoderms, suggesting that low extinction rates may be one of the reasons that ophiuroids are species-rich. The mean rate of COI substitution in Ophioderma is three times slower than that of echinoids. Conclusions of previous mitochondrial DNA studies of ophiuroids that relied on echinoid calibrations to determine divergence times need to be revised.}, } @article {pmid35348760, year = {2022}, author = {Azuma, T and Pánek, T and Tice, AK and Kayama, M and Kobayashi, M and Miyashita, H and Suzaki, T and Yabuki, A and Brown, MW and Kamikawa, R}, title = {An Enigmatic Stramenopile Sheds Light on Early Evolution in Ochrophyta Plastid Organellogenesis.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35348760}, issn = {1537-1719}, mesh = {Ecosystem ; Evolution, Molecular ; *Genome, Plastid ; Phylogeny ; Plants/genetics ; Plastids/genetics ; *Stramenopiles/genetics ; }, abstract = {Ochrophyta is an algal group belonging to the Stramenopiles and comprises diverse lineages of algae which contribute significantly to the oceanic ecosystems as primary producers. However, early evolution of the plastid organelle in Ochrophyta is not fully understood. In this study, we provide a well-supported tree of the Stramenopiles inferred by the large-scale phylogenomic analysis that unveils the eukaryvorous (nonphotosynthetic) protist Actinophrys sol (Actinophryidae) is closely related to Ochrophyta. We used genomic and transcriptomic data generated from A. sol to detect molecular traits of its plastid and we found no evidence of plastid genome and plastid-mediated biosynthesis, consistent with previous ultrastructural studies that did not identify any plastids in Actinophryidae. Moreover, our phylogenetic analyses of particular biosynthetic pathways provide no evidence of a current and past plastid in A. sol. However, we found more than a dozen organellar aminoacyl-tRNA synthases (aaRSs) that are of algal origin. Close relationships between aaRS from A. sol and their ochrophyte homologs document gene transfer of algal genes that happened before the divergence of Actinophryidae and Ochrophyta lineages. We further showed experimentally that organellar aaRSs of A. sol are targeted exclusively to mitochondria, although organellar aaRSs in Ochrophyta are dually targeted to mitochondria and plastids. Together, our findings suggested that the last common ancestor of Actinophryidae and Ochrophyta had not yet completed the establishment of host-plastid partnership as seen in the current Ochrophyta species, but acquired at least certain nuclear-encoded genes for the plastid functions.}, } @article {pmid35342946, year = {2022}, author = {Senarat, S and Kettratad, J and Pairohakul, S and Ampawong, S and Huggins, BP and Coleman, MM and Kaneko, G}, title = {An update on the evolutionary origin of aglomerular kidney with structural and ultrastructural descriptions of the kidney in three fish species.}, journal = {Journal of fish biology}, volume = {100}, number = {5}, pages = {1283-1298}, doi = {10.1111/jfb.15045}, pmid = {35342946}, issn = {1095-8649}, mesh = {Animals ; *Batrachoidiformes ; Kidney/ultrastructure ; Kidney Glomerulus/ultrastructure ; Kidney Tubules ; Nephrons/ultrastructure ; *Smegmamorpha ; }, abstract = {The kidney of fish contains numerous nephrons, each of which is divided into the renal corpuscle and renal tubules. This glomerular structure is the filtration unit of the nephron and is important for the kidney function, but it has been reported that the renal corpuscle was lost in at least four independent linages of fish (i.e., aglomerular kidney). In this study, the authors newly described renal structures for three species by histological and ultrastructural observations: two aglomerular kidneys from a seahorse Hippocampus barbouri and a toadfish Allenbatrachus grunniens and a glomerular kidney from a snake eel Pisodonophis boro. The renal development of H. barbouri was also described during 1-35 days after birth. In all species tested, the anterior kidney was comprised of haematopoietic tissues and a few renal tubules, whereas the posterior kidney contained more renal tubules. Although the glomerular structure was present in P. boro, light microscopic observations identified no glomeruli in the kidney of H. barbouri and A. grunniens. Ultrastructurally, abundant deep basal infoldings with mitochondria in the renal tubules were observed in A. grunniens compared to H. barbouri and P. boro, suggesting the possible role of basal infoldings in maintaining the osmotic balance. By integrating the results from the three species and comprehensive literature search, the authors further showed that 56 species have been reported to be aglomerular, and that the aglomerular kidney has evolved at least eight times in bony fishes.}, } @article {pmid35340599, year = {2022}, author = {Hickey, T and Devaux, J and Rajagopal, V and Power, A and Crossman, D}, title = {Paradoxes of Hymenoptera flight muscles, extreme machines.}, journal = {Biophysical reviews}, volume = {14}, number = {1}, pages = {403-412}, pmid = {35340599}, issn = {1867-2450}, abstract = {In the Carboniferous, insects evolved flight. Intense selection drove for high performance and approximately 100 million years later, Hymenoptera (bees, wasps and ants) emerged. Some species had proportionately small wings, with apparently impossible aerodynamic challenges including a need for high frequency flight muscles (FMs), powered exclusively off aerobic pathways and resulting in extreme aerobic capacities. Modern insect FMs are the most refined and form large dense blocks that occupy 90% of the thorax. These can beat wings at 200 to 230 Hz, more than double that achieved by standard neuromuscular systems. To do so, rapid repolarisation was circumvented through evolution of asynchronous stimulation, stretch activation, elastic recoil and a paradoxically slow Ca[2+] reuptake. While the latter conserves ATP, considerable ATP is demanded at the myofibrils. FMs have diminished sarcoplasmic volumes, and ATP is produced solely by mitochondria, which pack myocytes to maximal limits and have very dense cristae. Gaseous oxygen is supplied directly to mitochondria. While FMs appear to be optimised for function, several unusual paradoxes remain. FMs lack any significant equivalent to the creatine kinase shuttle, and myofibrils are twice as wide as those of within cardiomyocytes. The mitochondrial electron transport systems also release large amounts of reactive oxygen species (ROS) and respiratory complexes do not appear to be present at any exceptional level. Given that the loss of the creatine kinase shuttle and elevated ROS impairs heart function, we question how do FM shuttle adenylates at high rates and tolerate oxidative stress conditions that occur in diseased hearts?}, } @article {pmid35333655, year = {2022}, author = {Jackson, TD and Crameri, JJ and Muellner-Wong, L and Frazier, AE and Palmer, CS and Formosa, LE and Hock, DH and Fujihara, KM and Stait, T and Sharpe, AJ and Thorburn, DR and Ryan, MT and Stroud, DA and Stojanovski, D}, title = {Sideroflexin 4 is a complex I assembly factor that interacts with the MCIA complex and is required for the assembly of the ND2 module.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {13}, pages = {e2115566119}, pmid = {35333655}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/metabolism ; *Electron Transport Complex I/metabolism ; Humans ; Membrane Proteins ; Mitochondria/genetics/metabolism ; *Mitochondrial Diseases/genetics ; Mitochondrial Proteins/genetics/metabolism ; Mutation ; }, abstract = {SignificanceMitochondria are double-membraned eukaryotic organelles that house the proteins required for generation of ATP, the energy currency of cells. ATP generation within mitochondria is performed by five multisubunit complexes (complexes I to V), the assembly of which is an intricate process. Mutations in subunits of these complexes, or the suite of proteins that help them assemble, lead to a severe multisystem condition called mitochondrial disease. We show that SFXN4, a protein that causes mitochondrial disease when mutated, assists with the assembly of complex I. This finding explains why mutations in SFXN4 cause mitochondrial disease and is surprising because SFXN4 belongs to a family of amino acid transporter proteins, suggesting that it has undergone a dramatic shift in function through evolution.}, } @article {pmid35325186, year = {2022}, author = {Ye, Z and Zhao, C and Raborn, RT and Lin, M and Wei, W and Hao, Y and Lynch, M}, title = {Genetic Diversity, Heteroplasmy, and Recombination in Mitochondrial Genomes of Daphnia pulex, Daphnia pulicaria, and Daphnia obtusa.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35325186}, issn = {1537-1719}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA, Mitochondrial/genetics ; Daphnia/genetics ; *Genome, Mitochondrial ; Heteroplasmy ; *Pulicaria/genetics ; Recombination, Genetic ; }, abstract = {Genetic variants of mitochondrial DNA at the individual (heteroplasmy) and population (polymorphism) levels provide insight into their roles in multiple cellular and evolutionary processes. However, owing to the paucity of genome-wide data at the within-individual and population levels, the broad patterns of these two forms of variation remain poorly understood. Here, we analyze 1,804 complete mitochondrial genome sequences from Daphnia pulex, Daphnia pulicaria, and Daphnia obtusa. Extensive heteroplasmy is observed in D. obtusa, where the high level of intraclonal divergence must have resulted from a biparental-inheritance event, and recombination in the mitochondrial genome is apparent, although perhaps not widespread. Global samples of D. pulex reveal remarkably low mitochondrial effective population sizes, <3% of those for the nuclear genome. In addition, levels of population diversity in mitochondrial and nuclear genomes are uncorrelated across populations, suggesting an idiosyncratic evolutionary history of mitochondria in D. pulex. These population-genetic features appear to be a consequence of background selection associated with highly deleterious mutations arising in the strongly linked mitochondrial genome, which is consistent with polymorphism and divergence data suggesting a predominance of strong purifying selection. Nonetheless, the fixation of mildly deleterious mutations in the mitochondrial genome also appears to be driving positive selection on genes encoded in the nuclear genome whose products are deployed in the mitochondrion.}, } @article {pmid35322502, year = {2022}, author = {Cantoni, D and Osborne, A and Taib, N and Thompson, G and Martín-Escolano, R and Kazana, E and Edrich, E and Brown, IR and Gribaldo, S and Gourlay, CW and Tsaousis, AD}, title = {Localization and functional characterization of the alternative oxidase in Naegleria.}, journal = {The Journal of eukaryotic microbiology}, volume = {69}, number = {4}, pages = {e12908}, pmid = {35322502}, issn = {1550-7408}, support = {BB/M009971/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Eukaryota ; Mitochondrial Proteins ; *Naegleria ; *Naegleria fowleri ; Oxidoreductases/metabolism ; Plant Proteins ; }, abstract = {The alternative oxidase (AOX) is a protein involved in supporting enzymatic reactions of the Krebs cycle in instances when the canonical (cytochrome-mediated) respiratory chain has been inhibited, while allowing for the maintenance of cell growth and necessary metabolic processes for survival. Among eukaryotes, alternative oxidases have dispersed distribution and are found in plants, fungi, and protists, including Naegleria ssp. Naegleria species are free-living unicellular amoeboflagellates and include the pathogenic species of N. fowleri, the so-called "brain-eating amoeba." Using a multidisciplinary approach, we aimed to understand the evolution, localization, and function of AOX and the role that plays in Naegleria's biology. Our analyses suggest that AOX was present in last common ancestor of the genus and structure prediction showed that all functional residues are also present in Naegleria species. Using cellular and biochemical techniques, we also functionally characterize N. gruberi's AOX in its mitochondria, and we demonstrate that its inactivation affects its proliferation. Consequently, we discuss the benefits of the presence of this protein in Naegleria species, along with its potential pathogenicity role in N. fowleri. We predict that our findings will spearhead new explorations to understand the cell biology, metabolism, and evolution of Naegleria and other free-living relatives.}, } @article {pmid35318703, year = {2022}, author = {Hammond, M and Dorrell, RG and Speijer, D and Lukeš, J}, title = {Eukaryotic cellular intricacies shape mitochondrial proteomic complexity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {44}, number = {5}, pages = {e2100258}, doi = {10.1002/bies.202100258}, pmid = {35318703}, issn = {1521-1878}, mesh = {Biological Evolution ; Eukaryota/physiology ; *Eukaryotic Cells/metabolism ; Mitochondria/metabolism ; Organelles/metabolism ; Phylogeny ; *Proteomics ; }, abstract = {Mitochondria have been fundamental to the eco-physiological success of eukaryotes since the last eukaryotic common ancestor (LECA). They contribute essential functions to eukaryotic cells, above and beyond classical respiration. Mitochondria interact with, and complement, metabolic pathways occurring in other organelles, notably diversifying the chloroplast metabolism of photosynthetic organisms. Here, we integrate existing literature to investigate how mitochondrial metabolism varies across the landscape of eukaryotic evolution. We illustrate the mitochondrial remodelling and proteomic changes undergone in conjunction with major evolutionary transitions. We explore how the mitochondrial complexity of the LECA has been remodelled in specific groups to support subsequent evolutionary transitions, such as the acquisition of chloroplasts in photosynthetic species and the emergence of multicellularity. We highlight the versatile and crucial roles played by mitochondria during eukaryotic evolution, extending from its huge contribution to the development of the LECA itself to the dynamic evolution of individual eukaryote groups, reflecting both their current ecologies and evolutionary histories.}, } @article {pmid35307029, year = {2022}, author = {Smith, AJ and Advani, J and Brock, DC and Nellissery, J and Gumerson, J and Dong, L and Aravind, L and Kennedy, B and Swaroop, A}, title = {GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {68}, pmid = {35307029}, issn = {1741-7007}, support = {ZIAEY000450/EY/NEI NIH HHS/United States ; ZIAEY000546/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Gammaproteobacteria/metabolism ; *Glycation End Products, Advanced/metabolism ; Mammals ; Mice ; Mitochondrial Proteins/genetics ; Protein Deglycase DJ-1/metabolism ; }, abstract = {BACKGROUND: Functional complexity of the eukaryotic mitochondrial proteome is augmented by independent gene acquisition from bacteria since its endosymbiotic origins. Mammalian homologs of many ancestral mitochondrial proteins have uncharacterized catalytic activities. Recent forward genetic approaches attributed functions to proteins in established metabolic pathways, thereby limiting the possibility of identifying novel biology relevant to human disease. We undertook a bottom-up biochemistry approach to discern evolutionarily conserved mitochondrial proteins with catalytic potential.

RESULTS: Here, we identify a Parkinson-associated DJ-1/PARK7-like protein-glutamine amidotransferase-like class 1 domain-containing 3A (GATD3A), with bacterial evolutionary affinities although not from alphaproteobacteria. We demonstrate that GATD3A localizes to the mitochondrial matrix and functions as a deglycase. Through its amidolysis domain, GATD3A removes non-enzymatic chemical modifications produced during the Maillard reaction between dicarbonyls and amines of nucleotides and amino acids. GATD3A interacts with factors involved in mitochondrial mRNA processing and translation, suggestive of a role in maintaining integrity of important biomolecules through its deglycase activity. The loss of GATD3A in mice is associated with accumulation of advanced glycation end products (AGEs) and altered mitochondrial dynamics.

CONCLUSIONS: An evolutionary perspective helped us prioritize a previously uncharacterized but predicted mitochondrial protein GATD3A, which mediates the removal of early glycation intermediates. GATD3A restricts the formation of AGEs in mitochondria and is a relevant target for diseases where AGE deposition is a pathological hallmark.}, } @article {pmid35306886, year = {2022}, author = {Zluvova, J and Kubat, Z and Hobza, R and Janousek, B}, title = {Adaptive changes of the autosomal part of the genome in a dioecious clade of Silene.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {377}, number = {1850}, pages = {20210228}, pmid = {35306886}, issn = {1471-2970}, mesh = {Chromosomes, Plant ; Evolution, Molecular ; *Magnoliopsida ; Sex Chromosomes ; *Silene/genetics ; }, abstract = {The genus Silene brings many opportunities for the study of various processes involved in the evolution of dioecy and young sex chromosomes. Here we focus on a dioecious clade in Silene subgenus Silene and closely related species. This study provides improved support for monophyly of this clade (based on inclusion of further dioecious species) and a new estimate of its age (ca 2.3 million years). We observed a rise in adaptive evolution in the autosomal and pseudoautosomal parts of the genome on the branch where dioecy originated. This increase is not a result of the accumulation of sexually antagonistic genes in the pseudoautosomal region. It is also not caused by the coevolution of genes acting in mitochondria (despite the possibility that dioecy along this branch could have evolved from a nucleo-cytoplasmic male sterility-based system). After considering other possibilities, the most parsimonious explanation for the increase seen in the number of positively selected codons is the adaptive evolution of genes involved in the adaptation of the autosomal part of the genome to dioecy, as described in Charnov's sex-allocation theory. As the observed coincidence cannot prove causality, studies in other dioecious clades are necessary to allow the formation of general conclusions. This article is part of the theme issue 'Sex determination and sex chromosome evolution in land plants'.}, } @article {pmid35294555, year = {2022}, author = {Karmin, M and Flores, R and Saag, L and Hudjashov, G and Brucato, N and Crenna-Darusallam, C and Larena, M and Endicott, PL and Jakobsson, M and Lansing, JS and Sudoyo, H and Leavesley, M and Metspalu, M and Ricaut, FX and Cox, MP}, title = {Episodes of Diversification and Isolation in Island Southeast Asian and Near Oceanian Male Lineages.}, journal = {Molecular biology and evolution}, volume = {39}, number = {3}, pages = {}, pmid = {35294555}, issn = {1537-1719}, mesh = {Asia, Southeastern ; *Asian People ; *DNA, Mitochondrial/genetics ; Humans ; Male ; Mitochondria/genetics ; Phylogeny ; }, abstract = {Island Southeast Asia (ISEA) and Oceania host one of the world's richest assemblages of human phenotypic, linguistic, and cultural diversity. Despite this, the region's male genetic lineages are globally among the last to remain unresolved. We compiled ∼9.7 Mb of Y chromosome (chrY) sequence from a diverse sample of over 380 men from this region, including 152 first reported here. The granularity of this data set allows us to fully resolve and date the regional chrY phylogeny. This new high-resolution tree confirms two main population bursts: multiple rapid diversifications following the region's initial settlement ∼50 kya, and extensive expansions <6 kya. Notably, ∼40-25 kya the deep rooting local lineages of C-M130, M-P256, and S-B254 show almost no further branching events in ISEA, New Guinea, and Australia, matching a similar pause in diversification seen in maternal mitochondrial DNA lineages. The main local lineages start diversifying ∼25 kya, at the time of the last glacial maximum. This improved chrY topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and ISEA, potential interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape observed today formed. The high-resolution phylogeny of the chrY presented here thus enables a detailed exploration of past isolation, interaction, and change in one of the world's least understood regions.}, } @article {pmid35289381, year = {2022}, author = {Drechsel, V and Schneebauer, G and Sandbichler, AM and Fiechtner, B and Pelster, B}, title = {Oxygen consumption and acid secretion in isolated gas gland cells of the European eel Anguilla anguilla.}, journal = {Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology}, volume = {192}, number = {3-4}, pages = {447-457}, pmid = {35289381}, issn = {1432-136X}, mesh = {Air Sacs/metabolism ; *Anguilla/metabolism ; Animals ; Glucose/metabolism ; Oxygen/metabolism ; Oxygen Consumption ; }, abstract = {Swimbladder gas gland cells are known to produce lactic acid required for the acidification of swimbladder blood and decreasing the oxygen carrying capacity of swimbladder blood, i.e., the onset of the Root effect. Gas gland cells have also been shown to metabolize glucose via the pentose phosphate shunt, but the role of the pentose phosphate shunt for acid secretion has not yet been evaluated. Similarly, aerobic metabolism of gas gland cells has been largely neglected so far. In the present study, we therefore simultaneously assessed the role of glycolysis and of the pentose phosphate shunt for acid secretion and recorded oxygen consumption of isolated swimbladder gas gland cells of the European eel. Presence of glucose was essential for acid secretion, and at glucose concentrations of about 1.5 mmol l[-1] acid secretion of gas gland cells reached a maximum, indicating that glucose concentrations in swimbladder blood should not be limiting acid production and secretion under physiological conditions. The data revealed that most of the acid was produced in the glycolytic pathway, but a significant fraction was also contributed by the pentose phosphate shunt. Addition of glucose to gas gland cells incubated in a glucose-free medium resulted in a reduction of oxygen uptake. Inhibition of mitochondrial respiration significantly reduced oxygen consumption, but a fraction of mitochondria-independent respiration remained in presence of rotenone and antimycin A. In the presence of glucose, application of either iodo-acetate inhibiting glycolysis or 6-AN inhibiting the pentose phosphate shunt did not significantly affect oxygen uptake, indicating an independent regulation of oxidative phosphorylation and of acid production. Inhibition of the muscarinic acetylcholine receptor caused a slight elevation in acid secretion, while forskolin caused a concentration-dependent reduction in acid secretion, indicating muscarinic and c-AMP-dependent control of acid secretion in gas gland cells.}, } @article {pmid35279439, year = {2022}, author = {Zhou, B and Qi, D and Liu, S and Qi, H and Wang, Y and Zhao, K and Tian, F}, title = {Physiological, morphological and transcriptomic responses of Tibetan naked carps (Gymnocypris przewalskii) to salinity variations.}, journal = {Comparative biochemistry and physiology. Part D, Genomics & proteomics}, volume = {42}, number = {}, pages = {100982}, doi = {10.1016/j.cbd.2022.100982}, pmid = {35279439}, issn = {1878-0407}, mesh = {Animals ; *Carps ; *Cyprinidae/genetics ; Gills ; Lakes ; Salinity ; Tibet ; Transcriptome ; }, abstract = {Gymnocypris przewalskii is a native cyprinid fish that dwells in the Lake Qinghai with salinity of 12-13‰. It migrates annually to the freshwater rivers for spawning, experiencing the significant changes in salinity. In the present study, we performed the physiological, morphological and transcriptomic analyses to understand the osmoregulation in G. przewalskii. The physiological assay showed that the osmotic pressure of G. przewalskii was almost isosmotic to the brackish lake water. The low salinity reduced its ionic concentrations and osmotic pressure. The plasticity of gill microstructure was linked to the salinity variations, including the presence of mucus and intact tight junctions in brackish water and the development of the mitochondria-rich cells and the loosened tight junctions in freshwater. RNA-seq analysis identified 1926 differentially expressed genes, including 710 and 1216 down- and up-regulated genes in freshwater, which were enriched in ion transport, cell-cell adhesion, and mucus secretion. Genes in ion uptake were activated in low salinity, and mucus pathways and tight junction showed the higher transcription in brackish water. The isosmoticity between the body fluid and the environment suggested G. przewalskii was in the metabolic-saving condition in the brackish water. The decreased salinity disrupted this balance, which activated the ion uptake in freshwater to maintain osmotic homeostasis. The gill remodeling was involved in this process through the development of the mitochondria-rich cells to enhance ion uptake. The current finding provided insights into the potential mechanisms of G. przewalskii to cope with salinity alteration.}, } @article {pmid35277964, year = {2022}, author = {Lam, SM and Li, J and Sun, H and Mao, W and Lu, Z and Zhao, Q and Han, C and Gong, X and Jiang, B and Chua, GH and Zhao, Z and Meng, F and Shui, G}, title = {Quantitative Lipidomics and Spatial MS-Imaging Uncovered Neurological and Systemic Lipid Metabolic Pathways Underlying Troglomorphic Adaptations in Cave-Dwelling Fish.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35277964}, issn = {1537-1719}, mesh = {Animals ; Biological Evolution ; Caves ; *Characidae/genetics ; *Cyprinidae ; *Demyelinating Diseases ; Lipidomics ; Metabolic Networks and Pathways ; Phospholipids ; }, abstract = {Sinocyclocheilus represents a rare, freshwater teleost genus endemic to China that comprises the river-dwelling surface fish and the cave-dwelling cavefish. Using a combinatorial approach of quantitative lipidomics and mass-spectrometry imaging (MSI), we demonstrated that neural compartmentalization of lipid distribution and lipid metabolism is associated with the evolution of troglomorphic traits in Sinocyclocheilus. Attenuated docosahexaenoic acid (DHA) biosynthesis via the Δ4 desaturase pathway led to reductions in DHA-phospholipids in cavefish cerebellum. Instead, cavefish accumulates arachidonic acid-phospholipids that may disfavor retinotectal arbor growth. Importantly, MSI of sulfatides coupled with immunostaining of myelin basic protein and transmission electron microscopy images of hindbrain axons revealed demyelination in cavefish raphe serotonergic neurons. Demyelination in cavefish parallels the loss of neuroplasticity governing social behavior such as aggressive dominance. Outside the brain, quantitative lipidomics and qRT-PCR revealed systemic reductions in membrane esterified DHAs in the liver, attributed to suppression of genes along the Sprecher pathway (elovl2, elovl5, and acox1). Development of fatty livers was observed in cavefish; likely mediated by an impeded mobilization of storage lipids, as evident in the diminished expressions of pnpla2, lipea, lipeb, dagla, and mgll; and suppressed β-oxidation of fatty acyls via both mitochondria and peroxisomes as reflected in the reduced expressions of cpt1ab, hadhaa, cpt2, decr1, and acox1. These neurological and systemic metabolic adaptations serve to reduce energy expenditure, forming the basis of recessive evolution that eliminates nonessential morphological and behavioral traits and giving cavefish a selective advantage to thrive in caves where proper resource allocation becomes a major determinant of survival.}, } @article {pmid35272287, year = {2022}, author = {Ho, KM and Morgan, DJR}, title = {The Proximal Tubule as the Pathogenic and Therapeutic Target in Acute Kidney Injury.}, journal = {Nephron}, volume = {146}, number = {5}, pages = {494-502}, doi = {10.1159/000522341}, pmid = {35272287}, issn = {2235-3186}, mesh = {*Acute Kidney Injury/drug therapy/pathology ; Humans ; Kidney/pathology ; Kidney Glomerulus/pathology ; *Kidney Tubular Necrosis, Acute ; Kidney Tubules, Proximal/pathology ; }, abstract = {BACKGROUND: In 2004, the term acute kidney injury (AKI) was introduced with the intention of broadening our understanding of rapid declines in renal function and to replace the historical terms of acute renal failure and acute tubular necrosis (ATN). Despite this evolution in terminology, the mechanisms of AKI have stayed largely elusive with the pathophysiological concepts of ATN remaining the mainstay in our understanding of AKI.

SUMMARY: The proximal tubule (PT), having the highest mitochondrial content in the kidney and relying heavily on oxidative phosphorylation to generate ATP, is vulnerable to ischaemic insults and mitochondrial dysfunction. Histologically, pathological changes in the PT are more consistent than changes to the glomeruli or the loop of Henle in AKI. Physiologically, activation of tubuloglomerular feedback due to PT dysfunction leads to an increase in preglomerular afferent arteriole resistance and a reduction in glomerular filtration. Pharmacologically, frusemide - a drug commonly used in the setting of oliguric AKI - is actively secreted by the PT and its diuretic effect is compromised by its failure to be secreted into the urine and thus be delivered to its site of action at the loop of Henle in AKI. Increases in the urinary, but not plasma biomarkers, of PT injury within 1 h of shock suggest that the PT as the initiation pathogenic target of AKI.

KEY MESSAGE: Therapeutic agents targeting specifically the PT epithelial cells, in particular its mitochondria - including amino acid ergothioneine and superoxide scavenger MitoTEMPO - show great promises in ameliorating AKI.}, } @article {pmid35259985, year = {2022}, author = {Perez, M and Breusing, C and Angers, B and Beinart, RA and Won, YJ and Young, CR}, title = {Divergent paths in the evolutionary history of maternally transmitted clam symbionts.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1970}, pages = {20212137}, pmid = {35259985}, issn = {1471-2954}, mesh = {Animals ; Bacteria/genetics ; *Bivalvia/genetics ; *Gammaproteobacteria/genetics ; Genome Size ; Genome, Bacterial ; Phylogeny ; Symbiosis/genetics ; }, abstract = {Vertical transmission of bacterial endosymbionts is accompanied by virtually irreversible gene loss that results in a progressive reduction in genome size. While the evolutionary processes of genome reduction have been well described in some terrestrial symbioses, they are less understood in marine systems where vertical transmission is rarely observed. The association between deep-sea vesicomyid clams and chemosynthetic Gammaproteobacteria is one example of maternally inherited symbioses in the ocean. Here, we assessed the contributions of drift, recombination and selection to genome evolution in two extant vesicomyid symbiont clades by comparing 15 representative symbiont genomes (1.017-1.586 Mb) to those of closely related bacteria and the hosts' mitochondria. Our analyses suggest that drift is a significant force driving genome evolution in vesicomyid symbionts, though selection and interspecific recombination appear to be critical for maintaining symbiont functional integrity and creating divergent patterns of gene conservation. Notably, the two symbiont clades possess putative functional differences in sulfide physiology, anaerobic respiration and dependency on environmental vitamin B12, which probably reflect adaptations to different ecological habitats available to each symbiont group. Overall, these results contribute to our understanding of the eco-evolutionary processes shaping reductive genome evolution in vertically transmitted symbioses.}, } @article {pmid35258392, year = {2022}, author = {Magalhaes-Novais, S and Blecha, J and Naraine, R and Mikesova, J and Abaffy, P and Pecinova, A and Milosevic, M and Bohuslavova, R and Prochazka, J and Khan, S and Novotna, E and Sindelka, R and Machan, R and Dewerchin, M and Vlcak, E and Kalucka, J and Stemberkova Hubackova, S and Benda, A and Goveia, J and Mracek, T and Barinka, C and Carmeliet, P and Neuzil, J and Rohlenova, K and Rohlena, J}, title = {Mitochondrial respiration supports autophagy to provide stress resistance during quiescence.}, journal = {Autophagy}, volume = {18}, number = {10}, pages = {2409-2426}, pmid = {35258392}, issn = {1554-8635}, mesh = {AMP-Activated Protein Kinases/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; *Autophagy ; Cysteine/metabolism ; DNA, Mitochondrial/metabolism ; Dextrans/metabolism ; Endothelial Cells/metabolism ; Fibroblasts/metabolism ; Formaldehyde/metabolism ; Humans ; *Inflammatory Bowel Diseases/metabolism ; Isothiocyanates ; Lipopolysaccharides/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Microtubule-Associated Proteins/metabolism ; Mitochondria/metabolism ; Phosphatidylethanolamines/metabolism ; Reactive Oxygen Species/metabolism ; Respiration ; Sirolimus ; }, abstract = {Mitochondrial oxidative phosphorylation (OXPHOS) generates ATP, but OXPHOS also supports biosynthesis during proliferation. In contrast, the role of OXPHOS during quiescence, beyond ATP production, is not well understood. Using mouse models of inducible OXPHOS deficiency in all cell types or specifically in the vascular endothelium that negligibly relies on OXPHOS-derived ATP, we show that selectively during quiescence OXPHOS provides oxidative stress resistance by supporting macroautophagy/autophagy. Mechanistically, OXPHOS constitutively generates low levels of endogenous ROS that induce autophagy via attenuation of ATG4B activity, which provides protection from ROS insult. Physiologically, the OXPHOS-autophagy system (i) protects healthy tissue from toxicity of ROS-based anticancer therapy, and (ii) provides ROS resistance in the endothelium, ameliorating systemic LPS-induced inflammation as well as inflammatory bowel disease. Hence, cells acquired mitochondria during evolution to profit from oxidative metabolism, but also built in an autophagy-based ROS-induced protective mechanism to guard against oxidative stress associated with OXPHOS function during quiescence.Abbreviations: AMPK: AMP-activated protein kinase; AOX: alternative oxidase; Baf A: bafilomycin A1; CI, respiratory complexes I; DCF-DA: 2',7'-dichlordihydrofluorescein diacetate; DHE: dihydroethidium; DSS: dextran sodium sulfate; ΔΨmi: mitochondrial inner membrane potential; EdU: 5-ethynyl-2'-deoxyuridine; ETC: electron transport chain; FA: formaldehyde; HUVEC; human umbilical cord endothelial cells; IBD: inflammatory bowel disease; LC3B: microtubule associated protein 1 light chain 3 beta; LPS: lipopolysaccharide; MEFs: mouse embryonic fibroblasts; MTORC1: mechanistic target of rapamycin kinase complex 1; mtDNA: mitochondrial DNA; NAC: N-acetyl cysteine; OXPHOS: oxidative phosphorylation; PCs: proliferating cells; PE: phosphatidylethanolamine; PEITC: phenethyl isothiocyanate; QCs: quiescent cells; ROS: reactive oxygen species; PLA2: phospholipase A2, WB: western blot.}, } @article {pmid35255175, year = {2022}, author = {Treidel, LA and Quintanilla Ramirez, GS and Chung, DJ and Menze, MA and Vázquez-Medina, JP and Williams, CM}, title = {Selection on dispersal drives evolution of metabolic capacities for energy production in female wing-polymorphic sand field crickets, Gryllus firmus.}, journal = {Journal of evolutionary biology}, volume = {35}, number = {4}, pages = {599-609}, pmid = {35255175}, issn = {1420-9101}, mesh = {Animals ; Energy Metabolism ; Female ; *Gryllidae/physiology ; Phenotype ; Wings, Animal/metabolism ; }, abstract = {Life history and metabolism covary, but the mechanisms and individual traits responsible for these linkages remain unresolved. Dispersal capability is a critical component of life history that is constrained by metabolic capacities for energy production. Conflicting relationships between metabolism and life histories may be explained by accounting for variation in dispersal and maximal metabolic rates. We used female wing-polymorphic sand field crickets, Gryllus firmus, selected either for long wings (LW, flight-capable) or short wings (SW, flightless) to test the hypothesis that selection on dispersal capability drives the evolution of metabolic capacities. While resting metabolic rates were similar, long-winged crickets reached higher maximal metabolic rates than short-winged crickets, resulting in improved running performance. We further provided insight into the mechanisms responsible for covariation between life history and metabolism by comparing mitochondrial content of tissues involved in powering locomotion and assessing the function of mitochondria isolated from long- and short-winged crickets. Our results demonstrated that larger metabolic capacities in long-winged crickets were underpinned by increases in mitochondrial content of dorsoventral flight muscle and enhanced bioenergetic capacities of mitochondria within the fat body, a tissue responsible for fuel storage and mobilization. Thus, selection on flight capability correlates with increases in maximal, but not resting metabolic rates, through modifications of tissues powering locomotion at the cellular and organelle levels. This allows organisms to meet high energetic demands of activity for life history. Dispersal capability should therefore explicitly be considered as a potential factor driving the evolution of metabolic capacities.}, } @article {pmid35248958, year = {2022}, author = {Rodríguez-Martín, D and Murciano, A and Herráiz, M and de Francisco, P and Amaro, F and Gutiérrez, JC and Martín-González, A and Díaz, S}, title = {Arsenate and arsenite differential toxicity in Tetrahymena thermophila.}, journal = {Journal of hazardous materials}, volume = {431}, number = {}, pages = {128532}, doi = {10.1016/j.jhazmat.2022.128532}, pmid = {35248958}, issn = {1873-3336}, mesh = {Animals ; Arsenates/metabolism/toxicity ; *Arsenic/metabolism/toxicity ; *Arsenites/metabolism/toxicity ; Metallothionein ; *Tetrahymena thermophila/genetics ; }, abstract = {A comparative analysis of toxicities of both arsenic forms (arsenite and arsenate) in the model eukaryotic microorganism Tetrahymena thermophila (ciliate protozoa) has shown the presence of various detoxification mechanisms and cellular effects comparable to those of animal cells under arsenic stress. In the wild type strain SB1969 arsenate is almost 2.5 times more toxic than arsenite. According to the concentration addition model used in binary metallic mixtures their toxicities show an additive effect. Using fluorescent assays and flow cytometry, it has been detected that As(V) generates elevated levels of ROS/RNS compared to As(III). Both produce the same levels of superoxide anion, but As(V) also causes greater increases in hydrogen peroxide and peroxynitrite. The mitochondrial membrane potential is affected by both As(V) and As(III), and electron microscopy has also revealed that mitochondria are the main target of both arsenic ionic forms. Fusion/fission and swelling mitochondrial and mitophagy, together with macroautophagy, vacuolization and mucocyst extruction are mainly associated to As(V) toxicity, while As(III) induces an extensive lipid metabolism dysfunction (adipotropic effect). Quantitative RT-PCR analysis of some genes encoding antioxidant proteins or enzymes has shown that glutathione and thioredoxin metabolisms are involved in the response to arsenic stress. Likewise, the function of metallothioneins seems to be crucial in arsenic detoxification processes, after using both metallothionein knockout and knockdown strains and cells overexpressing metallothionein genes from this ciliate. The analysis of the differential toxicity of As(III) and As(V) shown in this study provides cytological and molecular tools to be used as biomarkers for each of the two arsenic ionic forms.}, } @article {pmid35247316, year = {2022}, author = {Moorthy, BT and Jiang, C and Patel, DM and Ban, Y and O'Shea, CR and Kumar, A and Yuan, T and Birnbaum, MD and Gomes, AV and Chen, X and Fontanesi, F and Lampidis, TJ and Barrientos, A and Zhang, F}, title = {The evolutionarily conserved arginyltransferase 1 mediates a pVHL-independent oxygen-sensing pathway in mammalian cells.}, journal = {Developmental cell}, volume = {57}, number = {5}, pages = {654-669.e9}, pmid = {35247316}, issn = {1878-1551}, support = {R01 GM138557/GM/NIGMS NIH HHS/United States ; R35 GM118141/GM/NIGMS NIH HHS/United States ; }, mesh = {*Aminoacyltransferases/genetics/metabolism ; Animals ; Humans ; Mammals/metabolism ; *Oxygen ; Phylogeny ; Proteolysis ; }, abstract = {The response to oxygen availability is a fundamental process concerning metabolism and survival/death in all mitochondria-containing eukaryotes. However, the known oxygen-sensing mechanism in mammalian cells depends on pVHL, which is only found among metazoans but not in other species. Here, we present an alternative oxygen-sensing pathway regulated by ATE1, an enzyme ubiquitously conserved in eukaryotes that influences protein degradation by posttranslational arginylation. We report that ATE1 centrally controls the hypoxic response and glycolysis in mammalian cells by preferentially arginylating HIF1α that is hydroxylated by PHD in the presence of oxygen. Furthermore, the degradation of arginylated HIF1α is independent of pVHL E3 ubiquitin ligase but dependent on the UBR family proteins. Bioinformatic analysis of human tumor data reveals that the ATE1/UBR and pVHL pathways jointly regulate oxygen sensing in a transcription-independent manner with different tissue specificities. Phylogenetic analysis suggests that eukaryotic ATE1 likely evolved during mitochondrial domestication, much earlier than pVHL.}, } @article {pmid35243551, year = {2022}, author = {Choi, H and Lee, K and Kim, D and Kim, S and Lee, JH}, title = {The implication of holocytochrome c synthase mutation in Korean familial hypoplastic amelogenesis imperfecta.}, journal = {Clinical oral investigations}, volume = {26}, number = {6}, pages = {4487-4498}, pmid = {35243551}, issn = {1436-3771}, mesh = {*Amelogenesis Imperfecta/genetics ; Dentists ; Humans ; Lyases ; Mutation ; Professional Role ; Republic of Korea ; }, abstract = {OBJECTIVES: This study aimed to comprehensively characterise genetic variants of amelogenesis imperfecta in a single Korean family through whole-exome sequencing and bioinformatics analysis.

MATERIAL AND METHODS: Thirty-one individuals of a Korean family, 9 of whom were affected and 22 unaffected by amelogenesis imperfecta, were enrolled. Whole-exome sequencing was performed on 12 saliva samples, including samples from 8 affected and 4 unaffected individuals. The possible candidate genes associated with the disease were screened by segregation analysis and variant filtering. In silico mutation impact analysis was then performed on the filtered variants based on sequence conservation and protein structure.

RESULTS: Whole-exome sequencing data revealed an X-linked dominant, heterozygous genomic missense mutation in the mitochondrial gene holocytochrome c synthase (HCCS). We also found that HCCS is potentially related to the role of mitochondria in amelogenesis. The HCCS variant was expected to be deleterious in both evolution-based and large population-based analyses. Further, the variant was predicted to have a negative effect on catalytic function of HCCS by in silico analysis of protein structure. In addition, HCCS had significant association with amelogenesis in literature mining analysis.

CONCLUSIONS: These findings suggest new evidence for the relationship between amelogenesis and mitochondria function, which could be implicated in the pathogenesis of amelogenesis imperfecta.

CLINICAL RELEVANCE: The discovery of HCCS mutations and a deeper understanding of the pathogenesis of amelogenesis imperfecta could lead to finding solutions for the fundamental treatment of this disease. Furthermore, it enables dental practitioners to establish predictable prosthetic treatment plans at an early stage by early detection of amelogenesis imperfecta through personalised medicine.}, } @article {pmid35242350, year = {2022}, author = {Pearman, WS and Wells, SJ and Dale, J and Silander, OK and Freed, NE}, title = {Long-read sequencing reveals atypical mitochondrial genome structure in a New Zealand marine isopod.}, journal = {Royal Society open science}, volume = {9}, number = {1}, pages = {211550}, pmid = {35242350}, issn = {2054-5703}, abstract = {Most animal mitochondrial genomes are small, circular and structurally conserved. However, recent work indicates that diverse taxa possess unusual mitochondrial genomes. In Isopoda, species in multiple lineages have atypical and rearranged mitochondrial genomes. However, more species of this speciose taxon need to be evaluated to understand the evolutionary origins of atypical mitochondrial genomes in this group. In this study, we report the presence of an atypical mitochondrial structure in the New Zealand endemic marine isopod, Isocladus armatus. Data from long- and short-read DNA sequencing suggest that I. armatus has two mitochondrial chromosomes. The first chromosome consists of two mitochondrial genomes that have been inverted and fused together in a circular form, and the second chromosome consists of a single mitochondrial genome in a linearized form. This atypical mitochondrial structure has been detected in other isopod lineages, and our data from an additional divergent isopod lineage (Sphaeromatidae) lends support to the hypothesis that atypical structure evolved early in the evolution of Isopoda. Additionally, we find that an asymmetrical site previously observed across many species within Isopoda is absent in I. armatus, but confirm the presence of two asymmetrical sites recently reported in two other isopod species.}, } @article {pmid35231030, year = {2022}, author = {Güngör, B and Flohr, T and Garg, SG and Herrmann, JM}, title = {The ER membrane complex (EMC) can functionally replace the Oxa1 insertase in mitochondria.}, journal = {PLoS biology}, volume = {20}, number = {3}, pages = {e3001380}, pmid = {35231030}, issn = {1545-7885}, mesh = {Amino Acid Sequence ; Cell Respiration/genetics ; Electron Transport Complex IV/genetics/*metabolism ; Endoplasmic Reticulum/*metabolism ; Membrane Proteins/genetics/*metabolism ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Mitochondrial Proton-Translocating ATPases/genetics/metabolism ; Mutation ; Nuclear Proteins/genetics/*metabolism ; Phylogeny ; Protein Biosynthesis/genetics ; Protein Transport/genetics ; Saccharomyces cerevisiae/genetics/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/classification/genetics/metabolism ; Sequence Homology, Amino Acid ; }, abstract = {Two multisubunit protein complexes for membrane protein insertion were recently identified in the endoplasmic reticulum (ER): the guided entry of tail anchor proteins (GET) complex and ER membrane complex (EMC). The structures of both of their hydrophobic core subunits, which are required for the insertion reaction, revealed an overall similarity to the YidC/Oxa1/Alb3 family members found in bacteria, mitochondria, and chloroplasts. This suggests that these membrane insertion machineries all share a common ancestry. To test whether these ER proteins can functionally replace Oxa1 in yeast mitochondria, we generated strains that express mitochondria-targeted Get2-Get1 and Emc6-Emc3 fusion proteins in Oxa1 deletion mutants. Interestingly, the Emc6-Emc3 fusion was able to complement an Δoxa1 mutant and restored its respiratory competence. The Emc6-Emc3 fusion promoted the insertion of the mitochondrially encoded protein Cox2, as well as of nuclear encoded inner membrane proteins, although was not able to facilitate the assembly of the Atp9 ring. Our observations indicate that protein insertion into the ER is functionally conserved to the insertion mechanism in bacteria and mitochondria and adheres to similar topological principles.}, } @article {pmid35222958, year = {2022}, author = {Zárate, D and Lima, TG and Poole, JD and Calfee, E and Burton, RS and Kohn, JR}, title = {Admixture in Africanized honey bees (Apis mellifera) from Panamá to San Diego, California (U.S.A.).}, journal = {Ecology and evolution}, volume = {12}, number = {2}, pages = {e8580}, pmid = {35222958}, issn = {2045-7758}, abstract = {The Africanized honey bee (AHB) is a New World amalgamation of several subspecies of the western honey bee (Apis mellifera), a diverse taxon historically grouped into four major biogeographic lineages: A (African), M (Western European), C (Eastern European), and O (Middle Eastern). In 1956, accidental release of experimentally bred "Africanized" hybrids from a research apiary in Sao Paulo, Brazil initiated a hybrid species expansion that now extends from northern Argentina to northern California (U.S.A.). Here, we assess nuclear admixture and mitochondrial ancestry in 60 bees from four countries (Panamá; Costa Rica, Mexico; U.S.A) across this expansive range to assess ancestry of AHB several decades following initial introduction and test the prediction that African ancestry decreases with increasing latitude. We find that AHB nuclear genomes from Central America and Mexico have predominately African genomes (76%-89%) with smaller contributions from Western and Eastern European lineages. Similarly, nearly all honey bees from Central America and Mexico possess mitochondrial ancestry from the African lineage with few individuals having European mitochondria. In contrast, AHB from San Diego (CA) shows markedly lower African ancestry (38%) with substantial genomic contributions from all four major honey bee lineages and mitochondrial ancestry from all four clades as well. Genetic diversity measures from all New World populations equal or exceed those of ancestral populations. Interestingly, the feral honey bee population of San Diego emerges as a reservoir of diverse admixture and high genetic diversity, making it a potentially rich source of genetic material for honey bee breeding.}, } @article {pmid35219813, year = {2022}, author = {Xia, L and Cheng, C and Zhao, X and He, X and Yu, X and Li, J and Wang, Y and Chen, J}, title = {Characterization of the mitochondrial genome of Cucumis hystrix and comparison with other cucurbit crops.}, journal = {Gene}, volume = {823}, number = {}, pages = {146342}, doi = {10.1016/j.gene.2022.146342}, pmid = {35219813}, issn = {1879-0038}, mesh = {Crops, Agricultural/genetics ; Cucumis/*genetics ; Cucurbitaceae/classification/*genetics ; Evolution, Molecular ; Gene Transfer, Horizontal ; Genome Size ; *Genome, Mitochondrial ; Genomics ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {The mitochondria ofCucumis genus contain several intriguing features such as paternal inheritance and three-ring genome structure. However, the evolutionary relationships of mitochondria inCucumisremain elusive. Here, we assembled the mitochondrial genome ofC. hystrixand performed a comparative genomic analysis with other crops inthe Cucurbitaceae. The mitochondrial genome ofC. hystrixhas three circular-mapping chromosomes of lengths 1,113,461 bp, 110,683 bp, and 92,288 bp, which contain 73 genes including 38 protein-coding genes, 31tRNAgenes, and 4rRNAgenes. Repeat sequences, RNA editing, and horizontal gene transfer events were identified. The results of phylogenetic analyses, collinearity and gene clusters revealed thatC. hystrixis closer toC. sativus than to C. melo. Meanwhile, wedemonstrated mitochondrial paternal inheritance inC. hystrixbymolecular markers. In comparison with other cucurbitcrops, wefound amarker foridentification of germplasm resources ofCucumis. Collectively, our findings provide a tool to help clarify the paternal lineage within that genus in the evolution of Cucumis.}, } @article {pmid35215562, year = {2022}, author = {Levy, D and Giannini, M and Oulehri, W and Riou, M and Marcot, C and Pizzimenti, M and Debrut, L and Charloux, A and Geny, B and Meyer, A}, title = {Long Term Follow-Up of Sarcopenia and Malnutrition after Hospitalization for COVID-19 in Conventional or Intensive Care Units.}, journal = {Nutrients}, volume = {14}, number = {4}, pages = {}, pmid = {35215562}, issn = {2072-6643}, mesh = {Aged ; *COVID-19/complications ; Follow-Up Studies ; Hand Strength ; Hospitalization ; Humans ; Intensive Care Units ; *Malnutrition/diagnosis/epidemiology ; Quality of Life ; SARS-CoV-2 ; *Sarcopenia/diagnosis/epidemiology/etiology ; }, abstract = {BACKGROUND: The post-COVID-19 condition, defined as COVID-19-related signs and symptoms lasting at least 2 months and persisting more than 3 months after infection, appears now as a public health issue in terms of frequency and quality of life alterations. Nevertheless, few data are available concerning long term evolution of malnutrition and sarcopenia, which deserve further attention.

METHOD: Sarcopenia was investigated prospectively, together with weight evolution, at admission and at 3 and 6 months after hospital discharge in 139 COVID-19 patients, using the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, associating both decreased muscle strength and muscle mass, assessed, respectively, with hand dynamometer and dual-energy X-ray absorptiometry.

RESULTS: Of the 139 patients, 22 presented with sarcopenia at 3 months; intensive care units (ICU) length of stay was the sole factor associated with sarcopenia after multivariate analysis. Although the entire group did not demonstrate significant weight change, weight decreased significantly in the sarcopenia group (Five and eight patients, showing, respectively, >5 or >10% weight decrease). Interestingly, at 6 months, 16 of the 22 patients recovered from sarcopenia and their weight returned toward baseline values.

CONCLUSIONS: Sarcopenia and malnutrition are frequently observed in patients hospitalized for COVID-19, even 3 months after infection occurrence, but can largely be reversed at 6 months after discharge. Enhanced patient care is needed in sarcopenic patients, particularly during long stays in an ICU.}, } @article {pmid35208909, year = {2022}, author = {Cevallos, MA and Degli Esposti, M}, title = {New Alphaproteobacteria Thrive in the Depths of the Ocean with Oxygen Gradient.}, journal = {Microorganisms}, volume = {10}, number = {2}, pages = {}, pmid = {35208909}, issn = {2076-2607}, abstract = {We survey here the Alphaproteobacteria, a large class encompassing physiologically diverse bacteria which are divided in several orders established since 2007. Currently, there is considerable uncertainty regarding the classification of an increasing number of marine metagenome-assembled genomes (MAGs) that remain poorly defined in their taxonomic position within Alphaproteobacteria. The traditional classification of NCBI taxonomy is increasingly complemented by the Genome Taxonomy Database (GTDB), but the two taxonomies differ considerably in the classification of several Alphaproteobacteria, especially from ocean metagenomes. We analyzed the classification of Alphaproteobacteria lineages that are most common in marine environments, using integrated approaches of phylogenomics and functional profiling of metabolic features that define their aerobic metabolism. Using protein markers such as NuoL, the largest membrane subunit of complex I, we have identified new clades of Alphaproteobacteria that are specific to marine niches with steep oxygen gradients (oxycline). These bacteria have relatives among MAGs found in anoxic strata of Lake Tanganyika and together define a lineage that is distinct from either Rhodospirillales or Sneathiellales. We characterized in particular the new 'oxycline' clade. Our analysis of Alphaproteobacteria also reveals new clues regarding the ancestry of mitochondria, which likely evolved in oxycline marine environments.}, } @article {pmid35207539, year = {2022}, author = {Lei, L and Burton, ZF}, title = {"Superwobbling" and tRNA-34 Wobble and tRNA-37 Anticodon Loop Modifications in Evolution and Devolution of the Genetic Code.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35207539}, issn = {2075-1729}, abstract = {The genetic code evolved around the reading of the tRNA anticodon on the primitive ribosome, and tRNA-34 wobble and tRNA-37 modifications coevolved with the code. We posit that EF-Tu, the closing mechanism of the 30S ribosomal subunit, methylation of wobble U34 at the 5-carbon and suppression of wobbling at the tRNA-36 position were partly redundant and overlapping functions that coevolved to establish the code. The genetic code devolved in evolution of mitochondria to reduce the size of the tRNAome (all of the tRNAs of an organism or organelle). "Superwobbling" or four-way wobbling describes a major mechanism for shrinking the mitochondrial tRNAome. In superwobbling, unmodified wobble tRNA-U34 can recognize all four codon wobble bases (A, G, C and U), allowing a single unmodified tRNA-U34 to read a 4-codon box. During code evolution, to suppress superwobbling in 2-codon sectors, U34 modification by methylation at the 5-carbon position appears essential. As expected, at the base of code evolution, tRNA-37 modifications mostly related to the identity of the adjacent tRNA-36 base. TRNA-37 modifications help maintain the translation frame during elongation.}, } @article {pmid35205291, year = {2022}, author = {Zhang, BQ and Song, XP and Zhang, XQ and Huang, YX and Liang, YJ and Zhou, S and Yang, CF and Yang, LT and Huang, X and Li, YR}, title = {Differential Gene Expression Analysis of SoCBL Family Calcineurin B-like Proteins: Potential Involvement in Sugarcane Cold Stress.}, journal = {Genes}, volume = {13}, number = {2}, pages = {}, pmid = {35205291}, issn = {2073-4425}, mesh = {Calcineurin/genetics ; Cold-Shock Response/genetics ; Gene Expression ; Phylogeny ; *Saccharum/genetics ; }, abstract = {Sugarcan e is a major crop for sugar and biofuel production and is cultivated in tropical and subtropical areas worldwide. Sugarcane growth is constrained because of winter's low-temperature stress, and cold resistance is an important limitation in sugarcane growth enhancement. Therefore, in this study, we identified a gene involved in the low-temperature stress response of sugarcane. Calcineurin B-like (CBL) protein is a calcium signal receptor involved in the cold stress response. Five sugarcane CBL genes were cloned, sequenced, and named SoCBL1, SoCBL3, SoCBL5, SoCBL6, and SoCBL9. The protein sequences of these genes were analyzed. The calculated molecular weight of these proteins was 24.5, 25.9, 25.2, 25.6, and 26.3 kD, respectively. Subcellular localization analysis revealed that SoCBL1, SoCBL3, SoCBL6, and SoCBL9 were situated in the cytoplasm, while SoCBL5 was present in mitochondria. Secondary structure analysis showed that these five CBL proteins had similar secondary structures. Conserved domain analysis displayed that each sugarcane CBL protein contained three conserved EF domains. According to the self-expanding values of the phylogenetic tree, the CBL gene family was divided into four groups. The CBL1 and CBL9 genes were classified into one group, illustrating that these two genes might possess a similar function. The expression analysis of the SoCBL gene under low temperatures showed that SoCBL3 and SoCBL5 were affected significantly, while SoCBL1 and SoCBL9 were less affected. These results demonstrate that the CBL genes in sugarcane have similar characteristics and present differences in genetic diversity and gene expression response to low temperatures. Therefore, these genes might be novel candidates for fighting cold stress in sugarcane.}, } @article {pmid35205149, year = {2022}, author = {Zhu, Y}, title = {Gap Junction-Dependent and -Independent Functions of Connexin43 in Biology.}, journal = {Biology}, volume = {11}, number = {2}, pages = {}, pmid = {35205149}, issn = {2079-7737}, abstract = {For the first time in animal evolution, the emergence of gap junctions allowed direct exchanges of cellular substances for communication between two cells. Innexin proteins constituted primordial gap junctions until the connexin protein emerged in deuterostomes and took over the gap junction function. After hundreds of millions of years of gene duplication, the connexin gene family now comprises 21 members in the human genome. Notably, GJA1, which encodes the Connexin43 protein, is one of the most widely expressed and commonly studied connexin genes. The loss of Gja1 in mice leads to swelling and a blockage of the right ventricular outflow tract and death of the embryos at birth, suggesting a vital role of Connexin43 gap junction in heart development. Since then, the importance of Connexin43-mediated gap junction function has been constantly expanded to other types of cells. Other than forming gap junctions, Connexin43 can also form hemichannels to release or uptake small molecules from the environment or even mediate many physiological processes in a gap junction-independent manner on plasma membranes. Surprisingly, Connexin43 also localizes to mitochondria in the cell, playing important roles in mitochondrial potassium import and respiration. At the molecular level, Connexin43 mRNA and protein are processed with very distinct mechanisms to yield carboxyl-terminal fragments with different sizes, which have their unique subcellular localization and distinct biological activities. Due to many exciting advancements in Connexin43 research, this review aims to start with a brief introduction of Connexin43 and then focuses on updating our knowledge of its gap junction-independent functions.}, } @article {pmid35199143, year = {2022}, author = {Helmstetter, N and Chybowska, AD and Delaney, C and Da Silva Dantas, A and Gifford, H and Wacker, T and Munro, C and Warris, A and Jones, B and Cuomo, CA and Wilson, D and Ramage, G and Farrer, RA}, title = {Population genetics and microevolution of clinical Candida glabrata reveals recombinant sequence types and hyper-variation within mitochondrial genomes, virulence genes, and drug targets.}, journal = {Genetics}, volume = {221}, number = {1}, pages = {}, pmid = {35199143}, issn = {1943-2631}, mesh = {Adult ; Antifungal Agents/pharmacology ; *Candida glabrata/genetics ; Drug Resistance, Fungal/genetics ; Genetics, Population ; *Genome, Mitochondrial ; Humans ; Virulence/genetics ; }, abstract = {Candida glabrata is the second most common etiological cause of worldwide systemic candidiasis in adult patients. Genome analysis of 68 isolates from 8 hospitals across Scotland, together with 83 global isolates, revealed insights into the population genetics and evolution of C. glabrata. Clinical isolates of C. glabrata from across Scotland are highly genetically diverse, including at least 19 separate sequence types that have been recovered previously in globally diverse locations, and 1 newly discovered sequence type. Several sequence types had evidence for ancestral recombination, suggesting transmission between distinct geographical regions has coincided with genetic exchange arising in new clades. Three isolates were missing MATα1, potentially representing a second mating type. Signatures of positive selection were identified in every sequence type including enrichment for epithelial adhesins thought to facilitate fungal adhesin to human epithelial cells. In patent microevolution was identified from 7 sets of recurrent cases of candidiasis, revealing an enrichment for nonsynonymous and frameshift indels in cell surface proteins. Microevolution within patients also affected epithelial adhesins genes, and several genes involved in drug resistance including the ergosterol synthesis gene ERG4 and the echinocandin target FKS1/2, the latter coinciding with a marked drop in fluconazole minimum inhibitory concentration. In addition to nuclear genome diversity, the C. glabrata mitochondrial genome was particularly diverse, with reduced conserved sequence and conserved protein-encoding genes in all nonreference ST15 isolates. Together, this study highlights the genetic diversity within the C. glabrata population that may impact virulence and drug resistance, and 2 major mechanisms generating this diversity: microevolution and genetic exchange/recombination.}, } @article {pmid35197365, year = {2022}, author = {Łabędzka-Dmoch, K and Rażew, M and Gapińska, M and Piątkowski, J and Kolondra, A and Salmonowicz, H and Wenda, JM and Nowotny, M and Golik, P}, title = {The Pet127 protein is a mitochondrial 5'-to-3' exoribonuclease from the PD-(D/E)XK superfamily involved in RNA maturation and intron degradation in yeasts.}, journal = {RNA (New York, N.Y.)}, volume = {28}, number = {5}, pages = {711-728}, pmid = {35197365}, issn = {1469-9001}, mesh = {Candida albicans ; *Exoribonucleases/genetics ; Fungal Proteins/genetics/metabolism ; Introns/genetics ; Mitochondrial Proteins/genetics ; Phylogeny ; *RNA ; }, abstract = {Pet127 is a mitochondrial protein found in multiple eukaryotic lineages, but absent from several taxa, including plants and animals. Distant homology suggests that it belongs to the divergent PD-(D/E)XK superfamily which includes various nucleases and related proteins. Earlier yeast genetics experiments suggest that it plays a nonessential role in RNA degradation and 5' end processing. Our phylogenetic analysis suggests that it is a primordial eukaryotic invention that was retained in diverse groups, and independently lost several times in the evolution of other organisms. We demonstrate for the first time that the fungal Pet127 protein in vitro is a processive 5'-to-3' exoribonuclease capable of digesting various substrates in a sequence nonspecific manner. Mutations in conserved residues essential in the PD-(D/E)XK superfamily active site abolish the activity of Pet127. Deletion of the PET127 gene in the pathogenic yeast Candida albicans results in a moderate increase in the steady-state levels of several transcripts and in accumulation of unspliced precursors and intronic sequences of three introns. Mutations in the active site residues result in a phenotype identical to that of the deletant, confirming that the exoribonuclease activity is related to the physiological role of the Pet127 protein. Pet127 activity is, however, not essential for maintaining the mitochondrial respiratory activity in C. albicans.}, } @article {pmid35191499, year = {2022}, author = {Zamudio-Ochoa, A and Morozov, YI and Sarfallah, A and Anikin, M and Temiakov, D}, title = {Mechanisms of mitochondrial promoter recognition in humans and other mammalian species.}, journal = {Nucleic acids research}, volume = {50}, number = {5}, pages = {2765-2781}, pmid = {35191499}, issn = {1362-4962}, support = {R35 GM131832/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA, Mitochondrial/genetics ; DNA-Directed RNA Polymerases/metabolism ; Humans ; Mammals/genetics/metabolism ; Mitochondria/enzymology/*genetics ; Mitochondrial Proteins/metabolism ; Transcription Factors/chemistry/genetics ; Transcription Initiation Site ; *Transcription, Genetic ; }, abstract = {Recognition of mammalian mitochondrial promoters requires the concerted action of mitochondrial RNA polymerase (mtRNAP) and transcription initiation factors TFAM and TFB2M. In this work, we found that transcript slippage results in heterogeneity of the human mitochondrial transcripts in vivo and in vitro. This allowed us to correctly interpret the RNAseq data, identify the bona fide transcription start sites (TSS), and assign mitochondrial promoters for > 50% of mammalian species and some other vertebrates. The divergent structure of the mammalian promoters reveals previously unappreciated aspects of mtDNA evolution. The correct assignment of TSS also enabled us to establish the precise register of the DNA in the initiation complex and permitted investigation of the sequence-specific protein-DNA interactions. We determined the molecular basis of promoter recognition by mtRNAP and TFB2M, which cooperatively recognize bases near TSS in a species-specific manner. Our findings reveal a role of mitochondrial transcription machinery in mitonuclear coevolution and speciation.}, } @article {pmid35189365, year = {2022}, author = {Hawlitschek, O and Ortiz, EM and Noori, S and Webster, KC and Husemann, M and Pereira, RJ}, title = {Transcriptomic data reveals nuclear-mitochondrial discordance in Gomphocerinae grasshoppers (Insecta: Orthoptera: Acrididae).}, journal = {Molecular phylogenetics and evolution}, volume = {170}, number = {}, pages = {107439}, doi = {10.1016/j.ympev.2022.107439}, pmid = {35189365}, issn = {1095-9513}, mesh = {Animals ; *Grasshoppers/genetics ; Hybridization, Genetic ; Mitochondria/genetics ; *Orthoptera/genetics ; Phylogeny ; Transcriptome ; }, abstract = {The phylogeny of many groups of Orthoptera remains poorly understood. Previous phylogenetic studies largely restricted to few mitochondrial markers found many species in the grasshopper subfamily Gomphocerinae to be para- or polyphyletic, presumably because of incomplete lineage sorting and ongoing hybridization between putatively young lineages. Resolving the phylogeny of the Chorthippus biguttulus species complex is important because many morphologically cryptic species occupy overlapping ranges across Eurasia and serve important ecological functions. We investigated whether multispecies coalescent analysis of 540 genes generated by transcriptome sequencing could resolve the phylogeny of the C. biguttulus complex and related Gomphocerinae species. Our divergence time estimates confirm that Gomphocerinae is a very young radiation, with an age estimated at 1.38 (2.35-0.77) mya for the C. biguttulus complex. Our estimated topology based on complete mitogenomes recovered some species as para- or polyphyletic. In contrast, the multispecies coalescent based on nuclear genes retrieved all species as monophyletic clusters, corroborating most taxonomic hypotheses. Our results underline the importance of using nuclear multispecies coalescent methods for studying young radiations and highlight the need of further taxonomic revision in Gomphocerinae grasshoppers.}, } @article {pmid35188099, year = {2022}, author = {De La Rossa, A and Laporte, MH and Astori, S and Marissal, T and Montessuit, S and Sheshadri, P and Ramos-Fernández, E and Mendez, P and Khani, A and Quairiaux, C and Taylor, EB and Rutter, J and Nunes, JM and Carleton, A and Duchen, MR and Sandi, C and Martinou, JC}, title = {Paradoxical neuronal hyperexcitability in a mouse model of mitochondrial pyruvate import deficiency.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35188099}, issn = {2050-084X}, mesh = {3-Hydroxybutyric Acid/pharmacology ; Animals ; Anion Transport Proteins/genetics/*metabolism ; Biological Transport ; Calcium/physiology ; Gene Expression Regulation/drug effects ; Homeostasis/drug effects/physiology ; Ketone Bodies ; Mice ; Mice, Knockout ; Mitochondria/*metabolism ; Mitochondrial Membrane Transport Proteins/genetics/*metabolism ; Monocarboxylic Acid Transporters/genetics/*metabolism ; Neurons/drug effects/metabolism ; Oxidation-Reduction ; Pentylenetetrazole/toxicity ; Phosphorylation ; Pyruvic Acid/*metabolism ; Seizures/chemically induced ; Tamoxifen/pharmacology ; }, abstract = {Neuronal excitation imposes a high demand of ATP in neurons. Most of the ATP derives primarily from pyruvate-mediated oxidative phosphorylation, a process that relies on import of pyruvate into mitochondria occuring exclusively via the mitochondrial pyruvate carrier (MPC). To investigate whether deficient oxidative phosphorylation impacts neuron excitability, we generated a mouse strain carrying a conditional deletion of MPC1, an essential subunit of the MPC, specifically in adult glutamatergic neurons. We found that, despite decreased levels of oxidative phosphorylation and decreased mitochondrial membrane potential in these excitatory neurons, mice were normal at rest. Surprisingly, in response to mild inhibition of GABA mediated synaptic activity, they rapidly developed severe seizures and died, whereas under similar conditions the behavior of control mice remained unchanged. We report that neurons with a deficient MPC were intrinsically hyperexcitable as a consequence of impaired calcium homeostasis, which reduced M-type potassium channel activity. Provision of ketone bodies restored energy status, calcium homeostasis and M-channel activity and attenuated seizures in animals fed a ketogenic diet. Our results provide an explanation for the seizures that frequently accompany a large number of neuropathologies, including cerebral ischemia and diverse mitochondriopathies, in which neurons experience an energy deficit.}, } @article {pmid35175958, year = {2022}, author = {Buja, LM}, title = {PATHOBIOLOGY OF MYOCARDIAL ISCHEMIA AND REPERFUSION INJURY: MODELS, MODES, MOLECULAR MECHANISMS, MODULATION AND CLINICAL APPLICATIONS.}, journal = {Cardiology in review}, volume = {}, number = {}, pages = {}, doi = {10.1097/CRD.0000000000000440}, pmid = {35175958}, issn = {1538-4683}, abstract = {This review presents an integrated approach to the analysis of myocardial ischemia and reperfusion injury and the modulating influence of myocardial conditioning during the evolution of acute myocardial infarction (AMI) and other clinical settings. Experimental studies have involved a spectrum of in vitro, ex vivo and in vivo models, and guidelines have been developed for the conduct of rigorous pre-clinical studies and for the identification of various forms of cell injury and death in evolving AMI. AMI in vivo is dominated by oncosis (cell injury with swelling) leading to necroptosis and final necrosis of ischemic cardiomyocytes (CMCs), without or with contraction band formation. Early after coronary occlusion, reperfusion salvages a significant amount of ischemic myocardium in the subepicardium while reperfusion injury contributes up to 50% of the final subendocardial infarct. AMI progression is mediated by damage (or danger)-associated molecular patterns (DAMPs), also known as alarmins, which activate pattern recognition receptors (PRRs) and initiate the inflammatory response. In pre-clinical studies, lethal reperfusion injury can largely be prevented with preconditioning or postconditioning by pharmacologic or physical means due to effects on both the CMC and microvasculature. Conditioning involves triggers, cytosolic mediators, and intracellular effectors. Mitochondria have a central role in the maintenance and loss of viability of CMCs. Reperfusion of severely ischemic myocardium leads to sustained opening of the mitochondrial permeability transition pore (MPTP). Once the MPTP is opened, the mitochondrial membrane potential (ΔΨm) is rapidly lost and energy production ceases. Conditioning blocks the sustained opening of the MPTP. Translation of conditioning strategies to the clinical management of patients has been challenging. The status of translation of experimental findings to approaches to modulate and ameliorate ischemic and reperfusion injury is discussed for the clinical settings of acute coronary syndromes (ACS) treated with percutaneous interventions (PCI) and cardiac preservation during open heart surgery and cardiac transplantation.}, } @article {pmid35174241, year = {2021}, author = {Ahmad, HI and Afzal, G and Iqbal, MN and Iqbal, MA and Shokrollahi, B and Mansoor, MK and Chen, J}, title = {Positive Selection Drives the Adaptive Evolution of Mitochondrial Antiviral Signaling (MAVS) Proteins-Mediating Innate Immunity in Mammals.}, journal = {Frontiers in veterinary science}, volume = {8}, number = {}, pages = {814765}, pmid = {35174241}, issn = {2297-1769}, abstract = {The regulated production of filamentous protein complexes is essential in many biological processes and provides a new paradigm in signal transmission. The mitochondrial antiviral signaling protein (MAVS) is a critical signaling hub in innate immunity that is activated when a receptor induces a shift in the globular caspase activation and recruitment domain of MAVS into helical superstructures (filaments). It is of interest whether adaptive evolution affects the proteins involved in innate immunity. Here, we explore and confer the role of selection and diversification on mitochondrial antiviral signaling protein in mammalian species. We obtined the MAVS proteins of mammalian species and examined their differences in evolutionary patterns. We discovered evidence for these proteins being subjected to substantial positive selection. We demonstrate that immune system proteins, particularly those encoding recognition proteins, develop under positive selection using codon-based probability methods. Positively chosen regions within recognition proteins cluster in domains involved in microorganism recognition, implying that molecular interactions between hosts and pathogens may promote adaptive evolution in the mammalian immune systems. These significant variations in MAVS development in mammalian species highlights the involvement of MAVS in innate immunity. Our findings highlight the significance of accounting for how non-synonymous alterations affect structure and function when employing sequence-level studies to determine and quantify positive selection.}, } @article {pmid35163839, year = {2022}, author = {Davoudi, M and Chen, J and Lou, Q}, title = {Genome-Wide Identification and Expression Analysis of Heat Shock Protein 70 (HSP70) Gene Family in Pumpkin (Cucurbita moschata) Rootstock under Drought Stress Suggested the Potential Role of these Chaperones in Stress Tolerance.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163839}, issn = {1422-0067}, mesh = {Cucurbita/genetics/*physiology ; *Down-Regulation ; Droughts ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant ; Genomics/*methods ; HSP70 Heat-Shock Proteins/*genetics ; Multigene Family ; Phylogeny ; Plant Proteins/genetics ; Promoter Regions, Genetic ; Selection, Genetic ; Stress, Physiological ; }, abstract = {Heat shock protein 70s (HSP70s) are highly conserved proteins that are involved in stress responses. These chaperones play pivotal roles in protein folding, removing the extra amounts of oxidized proteins, preventing protein denaturation, and improving the antioxidant system activities. This conserved family has been characterized in several crops under drought stress conditions. However, there is no study on HSP70s in pumpkin (Cucurbita moschata). Therefore, we performed a comprehensive analysis of this gene family, including phylogenetic relationship, motif and gene structure analysis, gene duplication, collinearity, and promoter analysis. In this research, we found 21 HSP70s that were classified into five groups (from A to E). These genes were mostly localized in the cytoplasm, chloroplast, mitochondria, nucleus, and endoplasmic reticulum (ER). We could observe more similarity in closely linked subfamilies in terms of motifs, the number of introns/exons, and the corresponding cellular compartments. According to the collinearity analysis, gene duplication had occurred as a result of purifying selection. The results showed that the occurrence of gene duplication for all nine gene pairs was due to segmental duplication (SD). Synteny analysis revealed a closer relationship between pumpkin and cucumber than pumpkin and Arabidopsis. Promoter analysis showed the presence of various cis-regulatory elements in the up-stream region of the HSP70 genes, such as hormones and stress-responsive elements, indicating a potential role of this gene family in stress tolerance. We furtherly performed the gene expression analysis of the HSP70s in pumpkin under progressive drought stress. Pumpkin is widely used as a rootstock to improve stress tolerance, as well as fruit quality of cucumber scion. Since stress-responsive mobile molecules translocate through vascular tissue from roots to the whole plant body, we used the xylem of grafted materials to study the expression patterns of the HSP70 (potentially mobile) gene family. The results indicated that all CmoHSP70s had very low expression levels at 4 days after stress (DAS). However, the genes showed different expression patterns by progressing he drought period. For example, the expression of CmoHSP70-4 (in subgroup E) and CmoHSP70-14 (in subgroup C) sharply increased at 6 and 11 DAS, respectively. However, the expression of all genes belonging to subgroup A did not change significantly in response to drought stress. These findings indicated the diverse roles of this gene family under drought stress and provided valuable information for further investigation on the function of this gene family, especially under stressful conditions.}, } @article {pmid35163579, year = {2022}, author = {Lin, YH and Lim, SN and Chen, CY and Chi, HC and Yeh, CT and Lin, WR}, title = {Functional Role of Mitochondrial DNA in Cancer Progression.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163579}, issn = {1422-0067}, mesh = {*DNA, Mitochondrial/genetics/metabolism ; *DNA, Neoplasm/genetics/metabolism ; Humans ; *Mitochondria/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; *Mutation ; Neoplasm Proteins/genetics/metabolism ; *Neoplasms/genetics/metabolism ; *Polymorphism, Single Nucleotide ; }, abstract = {Mitochondrial DNA (mtDNA) has been identified as a significant genetic biomarker in disease, cancer and evolution. Mitochondria function as modulators for regulating cellular metabolism. In the clinic, mtDNA variations (mutations/single nucleotide polymorphisms) and dysregulation of mitochondria-encoded genes are associated with survival outcomes among cancer patients. On the other hand, nuclear-encoded genes have been found to regulate mitochondria-encoded gene expression, in turn regulating mitochondrial homeostasis. These observations suggest that the crosstalk between the nuclear genome and mitochondrial genome is important for cellular function. Therefore, this review summarizes the significant mechanisms and functional roles of mtDNA variations (DNA level) and mtDNA-encoded genes (RNA and protein levels) in cancers and discusses new mechanisms of crosstalk between mtDNA and the nuclear genome.}, } @article {pmid35163574, year = {2022}, author = {Falchi, FA and Pizzoccheri, R and Briani, F}, title = {Activity and Function in Human Cells of the Evolutionary Conserved Exonuclease Polynucleotide Phosphorylase.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163574}, issn = {1422-0067}, mesh = {*Evolution, Molecular ; *Exoribonucleases/genetics/metabolism ; Humans ; *Mutation ; *RNA/genetics/metabolism ; *RNA Stability ; *RNA-Binding Proteins/genetics/metabolism ; }, abstract = {Polynucleotide phosphorylase (PNPase) is a phosphorolytic RNA exonuclease highly conserved throughout evolution. Human PNPase (hPNPase) is located in mitochondria and is essential for mitochondrial function and homeostasis. Not surprisingly, mutations in the PNPT1 gene, encoding hPNPase, cause serious diseases. hPNPase has been implicated in a plethora of processes taking place in different cell compartments and involving other proteins, some of which physically interact with hPNPase. This paper reviews hPNPase RNA binding and catalytic activity in relation with the protein structure and in comparison, with the activity of bacterial PNPases. The functions ascribed to hPNPase in different cell compartments are discussed, highlighting the gaps that still need to be filled to understand the physiological role of this ancient protein in human cells.}, } @article {pmid35163296, year = {2022}, author = {Amaroli, A and Ravera, S and Zekiy, A and Benedicenti, S and Pasquale, C}, title = {A Narrative Review on Oral and Periodontal Bacteria Microbiota Photobiomodulation, through Visible and Near-Infrared Light: From the Origins to Modern Therapies.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163296}, issn = {1422-0067}, mesh = {Bacteria ; Humans ; Infrared Rays ; Light ; Low-Level Light Therapy/methods/*trends ; Microbiota/*radiation effects ; Mitochondria ; Periodontal Diseases/*microbiology/radiotherapy ; Phototherapy/methods/trends ; Stomatitis/radiotherapy ; }, abstract = {Photobiomodulation (PBM) consists of a photon energy transfer to the cell, employing non-ionizing light sources belonging to the visible and infrared spectrum. PBM acts on some intrinsic properties of molecules, energizing them through specific light wavelengths. During the evolution of life, semiconducting minerals were energized by sun radiation. The molecules that followed became photoacceptors and were expressed into the first proto-cells and prokaryote membranes. Afterward, the components of the mitochondria electron transport chain influenced the eukaryotic cell physiology. Therefore, although many organisms have not utilized light as an energy source, many of the molecules involved in their physiology have retained their primordial photoacceptive properties. Thus, in this review, we discuss how PBM can affect the oral microbiota through photo-energization and the non-thermal effect of light on photoacceptors (i.e., cytochromes, flavins, and iron-proteins). Sometimes, the interaction of photons with pigments of an endogenous nature is followed by thermal or photodynamic-like effects. However, the preliminary data do not allow determining reliable therapies but stress the need for further knowledge on light-bacteria interactions and microbiota management in the health and illness of patients through PBM.}, } @article {pmid35162994, year = {2022}, author = {Phillips, MA and Arnold, KR and Vue, Z and Beasley, HK and Garza-Lopez, E and Marshall, AG and Morton, DJ and McReynolds, MR and Barter, TT and Hinton, A}, title = {Combining Metabolomics and Experimental Evolution Reveals Key Mechanisms Underlying Longevity Differences in Laboratory Evolved Drosophila melanogaster Populations.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35162994}, issn = {1422-0067}, mesh = {Aging/*genetics/metabolism ; Animals ; Carbohydrate Metabolism ; Citric Acid Cycle ; Directed Molecular Evolution ; Drosophila melanogaster/genetics/*physiology ; Genomics/*methods ; Longevity ; Metabolomics/*methods ; Mitochondria/metabolism ; Multifactorial Inheritance ; NAD/metabolism ; Polymorphism, Single Nucleotide ; }, abstract = {Experimental evolution with Drosophila melanogaster has been used extensively for decades to study aging and longevity. In recent years, the addition of DNA and RNA sequencing to this framework has allowed researchers to leverage the statistical power inherent to experimental evolution to study the genetic basis of longevity itself. Here, we incorporated metabolomic data into to this framework to generate even deeper insights into the physiological and genetic mechanisms underlying longevity differences in three groups of experimentally evolved D. melanogaster populations with different aging and longevity patterns. Our metabolomic analysis found that aging alters mitochondrial metabolism through increased consumption of NAD[+] and increased usage of the TCA cycle. Combining our genomic and metabolomic data produced a list of biologically relevant candidate genes. Among these candidates, we found significant enrichment for genes and pathways associated with neurological development and function, and carbohydrate metabolism. While we do not explicitly find enrichment for aging canonical genes, neurological dysregulation and carbohydrate metabolism are both known to be associated with accelerated aging and reduced longevity. Taken together, our results provide plausible genetic mechanisms for what might be driving longevity differences in this experimental system. More broadly, our findings demonstrate the value of combining multiple types of omic data with experimental evolution when attempting to dissect mechanisms underlying complex and highly polygenic traits such as aging.}, } @article {pmid35157851, year = {2022}, author = {Grass, M and McDougal, AD and Blazeski, A and Kamm, RD and García-Cardeña, G and Dewey, CF}, title = {A computational model of cardiomyocyte metabolism predicts unique reperfusion protocols capable of reducing cell damage during ischemia/reperfusion.}, journal = {The Journal of biological chemistry}, volume = {298}, number = {5}, pages = {101693}, pmid = {35157851}, issn = {1083-351X}, support = {T32 HL007627/HL/NHLBI NIH HHS/United States ; }, mesh = {*Computer Simulation ; Humans ; Ischemia/metabolism ; Mitochondria, Heart/metabolism ; *Myocardial Reperfusion Injury/metabolism ; *Myocytes, Cardiac/metabolism/pathology ; Oxygen/metabolism ; Reactive Oxygen Species/metabolism ; Reperfusion/*methods ; }, abstract = {If a coronary blood vessel is occluded and the neighboring cardiomyocytes deprived of oxygen, subsequent reperfusion of the ischemic tissue can lead to oxidative damage due to excessive generation of reactive oxygen species. Cardiomyocytes and their mitochondria are the main energy producers and consumers of the heart, and their metabolic changes during ischemia seem to be a key driver of reperfusion injury. Here, we hypothesized that tracking changes in cardiomyocyte metabolism, such as oxygen and ATP concentrations, would help in identifying points of metabolic failure during ischemia and reperfusion. To track some of these changes continuously from the onset of ischemia through reperfusion, we developed a system of differential equations representing the chemical reactions involved in the production and consumption of 67 molecular species. This model was validated and used to identify conditions present during periods of critical transition in ischemia and reperfusion that could lead to oxidative damage. These simulations identified a range of oxygen concentrations that lead to reverse mitochondrial electron transport at complex I of the respiratory chain and a spike in mitochondrial membrane potential, which are key suspects in the generation of reactive oxygen species at the onset of reperfusion. Our model predicts that a short initial reperfusion treatment with reduced oxygen content (5% of physiological levels) could reduce the cellular damage from both of these mechanisms. This model should serve as an open-source platform to test ideas for treatment of the ischemia reperfusion process by following the temporal evolution of molecular concentrations in the cardiomyocyte.}, } @article {pmid35148829, year = {2022}, author = {Loconte, V and Singla, J and Li, A and Chen, JH and Ekman, A and McDermott, G and Sali, A and Le Gros, M and White, KL and Larabell, CA}, title = {Soft X-ray tomography to map and quantify organelle interactions at the mesoscale.}, journal = {Structure (London, England : 1993)}, volume = {30}, number = {4}, pages = {510-521.e3}, pmid = {35148829}, issn = {1878-4186}, support = {P30 GM138441/GM/NIGMS NIH HHS/United States ; P41 GM103445/GM/NIGMS NIH HHS/United States ; P41 GM109824/GM/NIGMS NIH HHS/United States ; R01 GM083960/GM/NIGMS NIH HHS/United States ; }, mesh = {*Imaging, Three-Dimensional/methods ; Insulin ; Mitochondria/ultrastructure ; Organelles ; *Tomography, X-Ray/methods ; }, abstract = {Inter-organelle interactions are a vital part of normal cellular function; however, these have proven difficult to quantify due to the range of scales encountered in cell biology and the throughput limitations of traditional imaging approaches. Here, we demonstrate that soft X-ray tomography (SXT) can be used to rapidly map ultrastructural reorganization and inter-organelle interactions in intact cells. SXT takes advantage of the naturally occurring, differential X-ray absorption of the carbon-rich compounds in each organelle. Specifically, we use SXT to map the spatiotemporal evolution of insulin vesicles and their co-localization and interaction with mitochondria in pancreatic β cells during insulin secretion and in response to different stimuli. We quantify changes in the morphology, biochemical composition, and relative position of mitochondria and insulin vesicles. These findings highlight the importance of a comprehensive and unbiased mapping at the mesoscale to characterize cell reorganization that would be difficult to detect with other existing methodologies.}, } @article {pmid35145105, year = {2022}, author = {Elsemman, IE and Rodriguez Prado, A and Grigaitis, P and Garcia Albornoz, M and Harman, V and Holman, SW and van Heerden, J and Bruggeman, FJ and Bisschops, MMM and Sonnenschein, N and Hubbard, S and Beynon, R and Daran-Lapujade, P and Nielsen, J and Teusink, B}, title = {Whole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {801}, pmid = {35145105}, issn = {2041-1723}, support = {BB/M025748/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M025756/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Fermentation ; Gene Expression Regulation, Fungal ; Glucose/metabolism ; *Metabolic Networks and Pathways/genetics ; Mitochondria/metabolism ; Proteome/*metabolism ; *Proteomics ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Yeasts/*genetics/growth & development/*metabolism ; }, abstract = {When conditions change, unicellular organisms rewire their metabolism to sustain cell maintenance and cellular growth. Such rewiring may be understood as resource re-allocation under cellular constraints. Eukaryal cells contain metabolically active organelles such as mitochondria, competing for cytosolic space and resources, and the nature of the relevant cellular constraints remain to be determined for such cells. Here, we present a comprehensive metabolic model of the yeast cell, based on its full metabolic reaction network extended with protein synthesis and degradation reactions. The model predicts metabolic fluxes and corresponding protein expression by constraining compartment-specific protein pools and maximising growth rate. Comparing model predictions with quantitative experimental data suggests that under glucose limitation, a mitochondrial constraint limits growth at the onset of ethanol formation-known as the Crabtree effect. Under sugar excess, however, a constraint on total cytosolic volume dictates overflow metabolism. Our comprehensive model thus identifies condition-dependent and compartment-specific constraints that can explain metabolic strategies and protein expression profiles from growth rate optimisation, providing a framework to understand metabolic adaptation in eukaryal cells.}, } @article {pmid35143947, year = {2022}, author = {Sai Satyanarayana, D and Ahlawat, S and Sharma, R and Arora, R and Sharma, A and Tantia, MS and Vijh, RK}, title = {Mitochondrial DNA diversity divulges high levels of haplotype diversity and lack of genetic structure in the Indian camels.}, journal = {Gene}, volume = {820}, number = {}, pages = {146279}, doi = {10.1016/j.gene.2022.146279}, pmid = {35143947}, issn = {1879-0038}, mesh = {Animals ; Biodiversity ; Camelus/*genetics ; DNA, Mitochondrial/*genetics ; Female ; *Genetic Variation ; Haplotypes ; India ; Male ; Mitochondria/*genetics ; Phylogeny ; }, abstract = {Camels represent an important genetic resource of the desert ecosystems of India, with the dromedary and Bactrian camels inhabiting the hot and cold deserts, respectively. This study is the first attempt to investigate mitochondrial DNA based genetic diversity in the Indian camel populations and explores their relationship in the context of global genetic diversity of all the three large camel species (Camelus ferus, Camelus bactrianus and Camelus dromedaries). A mitochondrial DNA fragment encompassing part of cytochrome b gene, tRNA[Thr], tRNA[Pro] and the beginning of the control region was amplified and analyzed in 72 dromedary and 8 Bactrian camels of India. Sequence analysis revealed that the haplotype and nucleotide diversity (Hd: 0.937 and π: 0.00431) in the Indian dromedaries was higher than the indices reported so far for the dromedary or Bactrian camels across the globe. The corresponding values in the Indian Bactrian camels were 1.000 and 0.00393, respectively. Signals of population expansion were evident in the dromedaries of India on the basis of mismatch analysis and Fu's Fs values. The analysis of molecular variance attributed most of the genetic variance (92.15%) between the dromedary, wild Bactrian and domestic Bactrian camels indicating separate maternal origins. The existence of three mitochondrial lineages in the old world camels (C. bactrianus: Lineage A; C. ferus: Lineage B and C. dromedarius: Lineage C) was also substantiated by the topology of the Median-Joining network.}, } @article {pmid35135343, year = {2022}, author = {Horrell, HD and Lindeque, A and Farrell, AP and Seymour, RS and White, CR and Kruger, KM and Snelling, EP}, title = {Relationship between capillaries, mitochondria and maximum power of the heart: a meta-study from shrew to elephant.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1968}, pages = {20212461}, pmid = {35135343}, issn = {1471-2954}, mesh = {Animals ; *Capillaries ; *Elephants ; Humans ; Mitochondria ; Oxygen ; Oxygen Consumption ; Phylogeny ; Shrews ; }, abstract = {This meta-study uses phylogenetic scaling models across more than 30 species, spanning five orders of magnitude in body mass, to show that cardiac capillary numerical density and mitochondrial volume density decrease with body mass raised to the -0.07 ± 0.03 and -0.04 ± 0.01 exponents, respectively. Thus, while an average 10 g mammal has a cardiac capillary density of approximately 4150 mm[-2] and a mitochondrial density of 33%, a 1 t mammal has considerably lower corresponding values of 1850 mm[-2] and 21%. These similar scaling trajectories suggest quantitative matching for the primary oxygen supply and oxygen consuming structures of the heart, supporting economic design at the cellular level of the oxygen cascade in this aerobic organ. These scaling trajectories are nonetheless somewhat shallower than the exponent of -0.11 calculated for the maximum external mechanical power of the cardiac tissue, under conditions of heavy exercise, when oxygen flow between capillaries and mitochondria is probably fully exploited. This mismatch, if substantiated, implies a declining external mechanical efficiency of the heart with increasing body mass, whereby larger individuals put more energy in but get less energy out, a scenario with implications for cardiovascular design, aerobic capacity and limits of body size.}, } @article {pmid35133488, year = {2022}, author = {Shumenko, PG and Tatonova, YV}, title = {Assessing the population structure of trematode Metagonimus suifunensis using three mitochondrial markers.}, journal = {Parasitology research}, volume = {121}, number = {3}, pages = {915-923}, pmid = {35133488}, issn = {1432-1955}, mesh = {Animals ; DNA, Mitochondrial/chemistry/genetics ; Asia, Eastern ; Genetic Variation ; *Heterophyidae/genetics ; Mitochondria/genetics ; Phylogeny ; Russia ; }, abstract = {In this work, for the first time, the genetic variability of the Metagonimus suifunensis population in the Russian southern Far East was estimated based on the full-length sequences of the nad1 gene of mitochondrial DNA. In addition, for a sample of the same size, the sequences of cox1 and cytb genes, previously used for population studies for M. suifunensis, were reanalysed. Three markers were combined to a common sequence, and the obtained data were studied. Despite the higher level of variability, nad1 and cox1 mtDNA genes did not reveal subdivisions within the population. The combined dataset made it possible to determine that the sample from the Odyr River was the centre of the species' range formation and clarified the continental migration route of the parasite from south to north. According to the data obtained, it was presumed that piscivorous birds participate in the life cycle of the parasite. The subdivision within population revealed that using all three mitochondrial markers is consistent with the features of differentiation within populations of related species, but the reasons for its formation remain unclear due to the insufficient amount of data and the use of different markers in studies of different species.}, } @article {pmid35132109, year = {2022}, author = {Verma, RK and Kalyakulina, A and Mishra, A and Ivanchenko, M and Jalan, S}, title = {Role of mitochondrial genetic interactions in determining adaptation to high altitude human population.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {2046}, pmid = {35132109}, issn = {2045-2322}, mesh = {Adaptation, Physiological/*genetics ; *Altitude ; Epistasis, Genetic/*genetics ; Ethiopia ; Genes, Mitochondrial/*genetics/*physiology ; Humans ; Mitochondria/*genetics/*physiology ; Polymorphism, Genetic ; South America ; Tibet ; }, abstract = {Physiological and haplogroup studies performed to understand high-altitude adaptation in humans are limited to individual genes and polymorphic sites. Due to stochastic evolutionary forces, the frequency of a polymorphism is affected by changes in the frequency of a near-by polymorphism on the same DNA sample making them connected in terms of evolution. Here, first, we provide a method to model these mitochondrial polymorphisms as "co-mutation networks" for three high-altitude populations, Tibetan, Ethiopian and Andean. Then, by transforming these co-mutation networks into weighted and undirected gene-gene interaction (GGI) networks, we were able to identify functionally enriched genetic interactions of CYB and CO3 genes in Tibetan and Andean populations, while NADH dehydrogenase genes in the Ethiopian population playing a significant role in high altitude adaptation. These co-mutation based genetic networks provide insights into the role of different set of genes in high-altitude adaptation in human sub-populations.}, } @article {pmid35129136, year = {2022}, author = {Balasubramaniam, S and Soman, M and Katneni, VK and Tomy, S and Gopalapillay, G and Vijayan, KK}, title = {Mitochondrial DNA based diversity studies reveal distinct and substructured populations of pearlspot, Etroplus suratensis (Bloch, 1790) in Indian waters.}, journal = {Journal of genetics}, volume = {101}, number = {}, pages = {}, pmid = {35129136}, issn = {0973-7731}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; Genetic Variation ; Genetics, Population ; Haplotypes/genetics ; India ; *Mitochondria/genetics ; Phylogeny ; }, abstract = {Pearlspot (Etroplus suratensis) is one of the most commercially important brackish water fish species widely found along the coastal regions of peninsular India and Sri Lanka. Pearlspot is known for its tender flesh, delectable taste, culinary tourism and highyielding market value. Information on the genetic makeup of stocks/populations is extremely vital as it forms the basis for future genetic studies. For this, we utilized ATPase6/8 genes of mtDNA of pearlspot populations collected from nine different locations ranging from Ratnagiri in Maharashtra state on the west coast to Chilika in Odisha on the east coast. Sequence analyses of these genes revealed 33 polymorphic sites, which include 17 singleton and 16 parsimony informative sites. Pair-wise genetic differentiation study (FST = 0.75) indicated significant (P<0.001) differences among all the pairs of stocks except those from Chilika and Nagayalanka. The spatial analysis of molecular variance (SAMOVA) significantly delineated the population into four groups (FCT = 0.69, P = 0.0001), namely northwest (Ratnagiri and Goa); southwest (Mangalore and lakes at Vembanad, Ashtamudi and Vellayani in Kerala); southeast (Pulicat in Tamil Nadu) and northeast (Chilika in Odisha and Nagayalanka in Andhra Pradesh). The above delineation is supported by clades of the phylogenetic tree and also the clusters of median joining haplotype network. The high haplotype diversity (0.84), low nucleotide diversity (0.003), and negative values of Tajima's D (-1.47) and Fu's Fs statistic (-14.89) are characteristic of populations having recently undergone demographic expansion. Mantel test revealed significant isolation by distance. The study identifies highly delineated structured populations with restricted gene flow. If such a stock is overfished, it is highly unlikely that it would recover through migration. For any future breeding programme in this species, it would be desirable to form a base population which incorporates the genetic material from all the locations so that we get a wide gene pool to select from.}, } @article {pmid35122922, year = {2022}, author = {Baratange, C and Paris-Palacios, S and Bonnard, I and Delahaut, L and Grandjean, D and Wortham, L and Sayen, S and Gallorini, A and Michel, J and Renault, D and Breider, F and Loizeau, JL and Cosio, C}, title = {Metabolic, cellular and defense responses to single and co-exposure to carbamazepine and methylmercury in Dreissena polymorpha.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {300}, number = {}, pages = {118933}, doi = {10.1016/j.envpol.2022.118933}, pmid = {35122922}, issn = {1873-6424}, mesh = {Animals ; Carbamazepine/analysis/toxicity ; *Dreissena/metabolism ; Gills/metabolism ; *Methylmercury Compounds/metabolism/toxicity ; *Water Pollutants, Chemical/analysis ; }, abstract = {Carbamazepine (CBZ) and Hg are widespread and persistent micropollutants in aquatic environments. Both pollutants are known to trigger similar toxicity mechanisms, e.g. reactive oxygen species (ROS) production. Here, their effects were assessed in the zebra mussel Dreissena polymorpha, frequently used as a freshwater model in ecotoxicology and biomonitoring. Single and co-exposures to CBZ (3.9 μg L[-1]) and MeHg (280 ng L[-1]) were performed for 1 and 7 days. Metabolomics analyses evidenced that the co-exposure was the most disturbing after 7 days, reducing the amount of 25 metabolites involved in protein synthesis, energy metabolism, antioxidant response and osmoregulation, and significantly altering cells and organelles' structure supporting a reduction of functions of gills and digestive glands. CBZ alone after 7 days decreased the amount of α-aminobutyric acid and had a moderate effect on the structure of mitochondria in digestive glands. MeHg alone had no effect on mussels' metabolome, but caused a significant alteration of cells and organelles' structure in gills and digestive glands. Single exposures and the co-exposure increased antioxidant responses vs control in gills and digestive glands, without resulting in lipid peroxidation, suggesting an increased ROS production caused by both pollutants. Data globally supported that a higher number of hyperactive cells compensated cellular alterations in the digestive gland of mussels exposed to CBZ or MeHg alone, while CBZ + MeHg co-exposure overwhelmed this compensation after 7 days. Those effects were unpredictable based on cellular responses to CBZ and MeHg alone, highlighting the need to consider molecular toxicity pathways for a better anticipation of effects of pollutants in biota in complex environmental conditions.}, } @article {pmid35119574, year = {2022}, author = {Munekage, YN and Taniguchi, YY}, title = {A scheme for C4 evolution derived from a comparative analysis of the closely related C3, C3-C4 intermediate, C4-like, and C4 species in the genus Flaveria.}, journal = {Plant molecular biology}, volume = {110}, number = {4-5}, pages = {445-454}, pmid = {35119574}, issn = {1573-5028}, mesh = {*Flaveria/genetics ; Photosynthesis/physiology ; Mesophyll Cells ; Electron Transport ; Plants ; }, abstract = {A comparative analysis of the genus Flaveria showed a C4 evolutionary process in which the anatomical and metabolic features of C4 photosynthesis were gradually acquired through C3-C4 intermediate stages. C4 photosynthesis has been acquired in multiple lineages of angiosperms during evolution to suppress photorespiration. Crops that perform C4 photosynthesis exhibit high rates of CO2 assimilation and high grain production even under high-temperature in semiarid environments; therefore, engineering C4 photosynthesis in C3 plants is of great importance in the application field. The genus Flaveria contains a large number of C3, C3-C4 intermediate, C4-like, and C4 species, making it a good model genus to study the evolution of C4 photosynthesis, and these studies indicate the direction for C4 engineering. C4 photosynthesis was acquired gradually through the C3-C4 intermediate stage. First, a two-celled C2 cycle called C2 photosynthesis was acquired by localizing glycine decarboxylase activity in the mitochondria of bundle sheath cells. With the development of two-cell metabolism, anatomical features also changed. Next, the replacement of the two-celled C2 cycle by the two-celled C4 cycle was induced by the acquisition of cell-selective expression in addition to the upregulation of enzymes in the C4 cycle during the C3-C4 intermediate stage. This was supported by an increase in cyclic electron transport activity in response to an increase in the ATP/NADPH demand for metabolism. Suppression of the C3 cycle in mesophyll cells was induced after the functional establishment of the C4 cycle, and optimization of electron transport by suppressing the activity of photosystem II also occurred during the final phase of C4 evolution.}, } @article {pmid35113355, year = {2022}, author = {Singh, P and Lim, B}, title = {Targeting Apoptosis in Cancer.}, journal = {Current oncology reports}, volume = {24}, number = {3}, pages = {273-284}, pmid = {35113355}, issn = {1534-6269}, mesh = {*Antineoplastic Agents/pharmacology/therapeutic use ; Apoptosis ; Humans ; Mitochondria/metabolism ; *Neoplasms/drug therapy/metabolism ; Proto-Oncogene Proteins c-bcl-2 ; }, abstract = {PURPOSE OF REVIEW: Apoptosis is a major mechanism of cancer cell death. Thus, evasion of apoptosis results in therapy resistance. Here, we review apoptosis modulators in cancer and their recent developments, including MDM2 inhibitors and kinase inhibitors that can induce effective apoptosis.

RECENT FINDINGS: Both extrinsic pathways (external stimuli through cell surface death receptor) and intrinsic pathways (mitochondrial-mediated regulation upon genotoxic stress) regulate the complex process of apoptosis through orchestration of various proteins such as members of the BCL-2 family. Dysregulation within these complex steps can result in evasion of apoptosis. However, via the combined evolution of medicinal chemistry and molecular biology, omics assays have led to innovative inducers of apoptosis and inhibitors of anti-apoptotic regulators. Many of these agents are now being tested in cancer patients in early-phase trials. We believe that despite a sluggish speed of development, apoptosis targeting holds promise as a relevant strategy in cancer therapeutics.}, } @article {pmid35108076, year = {2022}, author = {Giannotti, D and Boscaro, V and Husnik, F and Vannini, C and Keeling, PJ}, title = {The "Other" Rickettsiales: an Overview of the Family "Candidatus Midichloriaceae".}, journal = {Applied and environmental microbiology}, volume = {88}, number = {6}, pages = {e0243221}, pmid = {35108076}, issn = {1098-5336}, mesh = {*Alphaproteobacteria/genetics ; Animals ; Bacteria ; Phylogeny ; *Rickettsiales ; Symbiosis ; }, abstract = {The family "Candidatus Midichloriaceae" constitutes the most diverse but least studied lineage within the important order of intracellular bacteria Rickettsiales. "Candidatus Midichloriaceae" endosymbionts are found in many hosts, including terrestrial arthropods, aquatic invertebrates, and protists. Representatives of the family are not documented to be pathogenic, but some are associated with diseased fish or corals. Different genera display a range of unusual features, such as full sets of flagellar genes without visible flagella or the ability to invade host mitochondria. Since studies on "Ca. Midichloriaceae" tend to focus on the host, the family is rarely addressed as a unit, and we therefore lack a coherent picture of its diversity. Here, we provide four new midichloriaceae genomes, and we survey molecular and ecological data from the entire family. Features like genome size, ecological context, and host transitions vary considerably even among closely related midichloriaceae, suggesting a high frequency of such shifts, incomplete sampling, or both. Important functional traits involved in energy metabolism, flagella, and secretion systems were independently reduced multiple times with no obvious correspondence to host or habitat, corroborating the idea that many features of these "professional symbionts" are largely independent of host identity. Finally, despite "Ca. Midichloriaceae" being predominantly studied in ticks, our analyses show that the clade is mainly aquatic, with a few terrestrial offshoots. This highlights the importance of considering aquatic hosts, and protists in particular, when reconstructing the evolution of these endosymbionts and by extension all Rickettsiales. IMPORTANCE Among endosymbiotic bacterial lineages, few are as intensely studied as Rickettsiales, which include the causative agents of spotted fever, typhus, and anaplasmosis. However, an important subgroup called "Candidatus Midichloriaceae" receives little attention despite accounting for a third of the diversity of Rickettsiales and harboring a wide range of bacteria with unique features, like the ability to infect mitochondria. Midichloriaceae are found in many hosts, from ticks to corals to unicellular protozoa, and studies on them tend to focus on the host groups. Here, for the first time since the establishment of this clade, we address the genomics, evolution, and ecology of "Ca. Midichloriaceae" as a whole, highlighting trends and patterns, the remaining gaps in our knowledge, and its importance for the understanding of symbiotic processes in intracellular bacteria.}, } @article {pmid35107193, year = {2022}, author = {Huisman, TAGM and Kralik, SF and Desai, NK and Serrallach, BL and Orman, G}, title = {Neuroimaging of primary mitochondrial disorders in children: A review.}, journal = {Journal of neuroimaging : official journal of the American Society of Neuroimaging}, volume = {32}, number = {2}, pages = {191-200}, doi = {10.1111/jon.12976}, pmid = {35107193}, issn = {1552-6569}, mesh = {Child ; Diagnosis, Differential ; Humans ; Mitochondria/metabolism ; *Mitochondrial Diseases/diagnostic imaging/genetics ; Neuroimaging/methods ; }, abstract = {Mitochondrial disorders represent a diverse and complex group of entities typified by defective energy metabolism. The mitochondrial oxidative phosphorylation system is typically impaired, which is the predominant source of energy production. Because mitochondria are present in nearly all organs, multiple systems may be affected including the central nervous system, skeletal muscles, kidneys, and liver. In particular, those organs that are metabolically active with high energy demands are explicitly vulnerable. Initial diagnostic work up relies on a detailed evaluation of clinical symptoms including physical examination as well as a comprehensive review of the evolution of symptoms over time, relation to possible "triggering" events (eg, fever, infection), blood workup, and family history. High-end neuroimaging plays a pivotal role in establishing diagnosis, narrowing differential diagnosis, monitoring disease progression, and predicting prognosis. The pattern and characteristics of the neuroimaging findings are often highly suggestive of a mitochondrial disorder; unfortunately, in many cases the wide variability of involved metabolic processes prevents a more specific subclassification. Consequently, additional diagnostic steps including muscle biopsy, metabolic workup, and genetic tests are necessary. In the current manuscript, basic concepts of energy production, genetics, and inheritance patterns are reviewed. In addition, the imaging findings of several illustrative mitochondrial disorders are presented to familiarize the involved physicians with pediatric mitochondrial disorders. In addition, the significance of spinal cord imaging and the value of "reversed image-based discovery" for the recognition and correct (re-)classification of mitochondrial disorders is discussed.}, } @article {pmid35104579, year = {2022}, author = {Gowri, P and Sathish, P and Mahesh Kumar, S and Sundaresan, P}, title = {Mutation profile of neurodegenerative mitochondriopathy - LHON in Southern India.}, journal = {Gene}, volume = {819}, number = {}, pages = {146202}, doi = {10.1016/j.gene.2022.146202}, pmid = {35104579}, issn = {1879-0038}, mesh = {Adolescent ; Adult ; Asian People/genetics ; Child ; Child, Preschool ; DNA, Mitochondrial/metabolism ; Female ; Genes, Mitochondrial ; Genetic Predisposition to Disease ; Genome, Mitochondrial ; Humans ; India ; Male ; Methylation ; Middle Aged ; Mitochondria/*genetics ; *Mutation ; Neurodegenerative Diseases/*genetics ; Optic Atrophy, Hereditary, Leber/*genetics ; Pedigree ; Phylogeny ; Young Adult ; }, abstract = {BACKGROUND: Leber's Hereditary Optic Neuropathy (LHON) is a rare mitochondriopathy causing retinal ganglion cell degeneration resulting in central vision loss. It is caused by mitochondrial DNA (mtDNA) mutations and thus follows maternal inheritance pattern.

METHODS: We analysed the whole mitochondrial genome in 100 South Indian LHON patients by utilizing Sanger and Next Generation Sequencing approaches. Haplogroup analysis was performed using HaploGrep2 to predict the risk group. Methylation changes in the mtDNA D-loop region were investigated by performing methylation-specific polymerase chain reaction (MSP).

RESULTS: LHON associated mutations were detected in 55% of the patients of which 42% harboured the primary mutations and 13% harboured potentially pathogenic variants that were previously reported to cause LHON. The candidate mutations identified with confirmed pathogenicity are: m.11778G > A (38%), m.14484 T > C (3%), m.4171C > A (1%) and m.11696G > A (1%). MSP results demonstrated that the D-loop region was unmethylated in all the study subjects including mutation-positive patients, mutation-negative patients, asymptomatic carriers, and controls. Haplogroup-M was prevalent (69%) in the study cohort followed by R (14%), U (9%), N (3%), HV (2%), G (2%), and W (1%). The frequency of the predominant mutation m.11778G > A was found lower (̴ 11%) in haplogroup-U.

CONCLUSIONS: South Indian LHON cohort shows a unique profile of mtDNA mutations and haplogroup association presumably with no role of D-loop methylation. MT-ND4, MT-ND5, and MT-ND1 serve as the hotspot genes in this cohort. The presence of LHON associated mutations in patients lacking the common primary mutations insists on the necessity of mitochondrial genome sequencing in individuals suspected with LHON.}, } @article {pmid35078356, year = {2022}, author = {Munasinghe, M and Haller, BC and Clark, AG}, title = {Migration restores hybrid incompatibility driven by mitochondrial-nuclear sexual conflict.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1967}, pages = {20212561}, pmid = {35078356}, issn = {1471-2954}, mesh = {Cell Nucleus/genetics ; Female ; *Genome, Mitochondrial ; Humans ; Male ; Mitochondria/genetics ; Mutation ; Reproductive Isolation ; }, abstract = {In the mitochondrial genome, sexual asymmetry in transmission allows the accumulation of male-harming mutations since selection acts only on the effect of the mutation in females. Called the 'Mother's Curse', this phenomenon induces a selective pressure for nuclear variants that compensate for this reduction in male fitness. Previous work has demonstrated the existence of these interactions and their potential to act as Dobzhansky-Muller incompatibilities, contributing to reproductive isolation between populations. However, it is not clear how readily they would give rise to and sustain hybrid incompatibilities. Here, we use computer simulations in SLiM 3 to investigate the consequences of sexually antagonistic mitochondrial-nuclear interactions in a subdivided population. We consider distinct migration schemes and vary the chromosomal location, and consequently the transmission pattern, of nuclear restorers. Disrupting these co-evolved interactions results in less-fit males, skewing the sex ratio toward females. Restoration of male fitness depends on both the chromosomal location of nuclear restorer loci and the migration scheme. Our results show that these interactions may act as Dobzhansky-Muller incompatibilities, but their strength is not enough to drive population isolation. Overall, this model shows the varied ways in which populations can respond to migration's disruption of co-evolved mitochondrial-nuclear interactions.}, } @article {pmid35077696, year = {2022}, author = {Smith, DR}, title = {Genome evolution: Minicircular mtDNA and unusual heteroplasmy in a parasitic plant.}, journal = {Current biology : CB}, volume = {32}, number = {2}, pages = {R86-R89}, doi = {10.1016/j.cub.2021.12.001}, pmid = {35077696}, issn = {1879-0445}, mesh = {*DNA, Mitochondrial/genetics ; *Genome, Mitochondrial/genetics ; Heteroplasmy ; Mitochondria/genetics ; Plants/genetics ; }, abstract = {Minicircular organelle genomes exist in diverse species but have never been observed in plants - that is, until now. The mitochondrial genome of the holoparasite Rhopalocnemis phalloides comprises 21 minicircles, which are extremely heteroplasmic, providing an exceptional example of convergent organelle evolution across disparate lineages.}, } @article {pmid35066390, year = {2022}, author = {Muthye, V and Mackereth, CD and Stewart, JB and Lavrov, DV}, title = {Large dataset of octocoral mitochondrial genomes provides new insights into mt-mutS evolution and function.}, journal = {DNA repair}, volume = {110}, number = {}, pages = {103273}, doi = {10.1016/j.dnarep.2022.103273}, pmid = {35066390}, issn = {1568-7856}, mesh = {Animals ; *Anthozoa/genetics ; DNA, Mitochondrial/chemistry/genetics ; Escherichia coli Proteins ; Evolution, Molecular ; *Genome, Mitochondrial ; MutS DNA Mismatch-Binding Protein/genetics ; Nucleotides ; Phylogeny ; }, abstract = {All studied octocoral mitochondrial genomes (mt-genomes) contain a homologue of the Escherichia coli mutS gene, a member of a gene family encoding proteins involved in DNA mismatch repair, other types of DNA repair, meiotic recombination, and other functions. Although mutS homologues are found in all domains of life, as well as viruses, octocoral mt-mutS is the only such gene found in an organellar genome. While the function of mtMutS is not known, its domain architecture, conserved sequence, and presence of several characteristic residues suggest its involvement in mitochondrial DNA repair. This inference is supported by exceptionally low rates of mt-sequence evolution observed in octocorals. Previous studies of mt-mutS have been limited by the small number of octocoral mt-genomes available. We utilized sequence-capture data from the recent Quattrini et al. 2020 study [Nature Ecology & Evolution 4:1531-1538] to assemble complete mt-genomes for 94 species of octocorals. Combined with sequences publicly available in GenBank, this resulted in a dataset of 184 complete mt-genomes, which we used to re-analyze the conservation and evolution of mt-mutS. In our analysis, we discovered the first case of mt-mutS loss among octocorals in one of the two Pseudoanthomastus spp. assembled from Quattrini et al. data. This species displayed accelerated rate and changed patterns of nucleotide substitutions in mt-genome, which we argue provide additional evidence for the role of mtMutS in DNA repair. In addition, we found accelerated mt-sequence evolution in the presence of mt-mutS in several octocoral lineages. This accelerated evolution did not appear to be the result of relaxed selection pressure and did not entail changes in patterns of nucleotide substitutions. Overall, our results support previously reported patterns of conservation in mt-mutS and suggest that mtMutS is involved in DNA repair in octocoral mitochondria. They also indicate that the presence of mt-mutS contributes to, but does not fully explain, the low rates of sequence evolution in octocorals.}, } @article {pmid35063045, year = {2022}, author = {Fan, Y and Zhang, Y and Rui, C and Zhang, H and Xu, N and Wang, J and Han, M and Lu, X and Chen, X and Wang, D and Wang, S and Guo, L and Zhao, L and Huang, H and Wang, J and Sun, L and Chen, C and Ye, W}, title = {Molecular structures and functional exploration of NDA family genes respond tolerant to alkaline stress in Gossypium hirsutum L.}, journal = {Biological research}, volume = {55}, number = {1}, pages = {4}, pmid = {35063045}, issn = {0717-6287}, mesh = {*Gene Expression Regulation, Plant ; Genome, Plant ; *Gossypium/genetics ; Molecular Structure ; Multigene Family/genetics ; Phylogeny ; Plant Proteins/genetics/metabolism ; Stress, Physiological/genetics ; }, abstract = {BACKGROUND: The internal NAD(P)H dehydrogenase (NDA) gene family was a member of the NAD(P)H dehydrogenase (ND) gene family, mainly involved in the non-phosphorylated respiratory pathways in mitochondria and played crucial roles in response to abiotic stress.

METHODS: The whole genome identification, structure analysis and expression pattern of NDA gene family were conducted to analyze the NDA gene family.

RESULTS: There were 51, 52, 26, and 24 NDA genes identified in G. hirsutum, G. barbadense, G. arboreum and G. raimondii, respectively. According to the structural characteristics of genes and traits of phylogenetic tree, we divided the NDA gene family into 8 clades. Gene structure analysis showed that the NDA gene family was relatively conservative. The four Gossypium species had good collinearity, and segmental duplication played an important role in the evolution of the NDA gene family. Analysis of cis-elements showed that most GhNDA genes contained cis-elements related to light response and plant hormones (ABA, MeJA and GA). The analysis of the expression patterns of GhNDA genes under different alkaline stress showed that GhNDA genes were actively involved in the response to alkaline stress, possibly through different molecular mechanisms. By analyzing the existing RNA-Seq data after alkaline stress, it was found that an NDA family gene GhNDA32 was expressed, and then theGhNDA32 was silenced by virus-induced gene silencing (VIGS). By observing the phenotype, we found that the wilting degree of silenced plants was much higher than that of the control plant after alkaline treatment, suggesting that GhNDA32 gene was involved in the response to alkaline stress.

CONCLUSIONS: In this study, GhNDAs participated in response to alkaline stress, especially NaHCO3 stress. It was of great significance for the future research on the molecular mechanism of NDA gene family in responding to abiotic stresses.}, } @article {pmid35061308, year = {2022}, author = {Choi, IS and Wojciechowski, MF and Steele, KP and Hunter, SG and Ruhlman, TA and Jansen, RK}, title = {Born in the mitochondrion and raised in the nucleus: evolution of a novel tandem repeat family in Medicago polymorpha (Fabaceae).}, journal = {The Plant journal : for cell and molecular biology}, volume = {110}, number = {2}, pages = {389-406}, doi = {10.1111/tpj.15676}, pmid = {35061308}, issn = {1365-313X}, mesh = {*Genome, Mitochondrial/genetics ; Genome, Plant/genetics ; *Medicago/genetics ; Mitochondria/genetics ; Tandem Repeat Sequences/genetics ; }, abstract = {Plant nuclear genomes harbor sequence elements derived from the organelles (mitochondrion and plastid) through intracellular gene transfer (IGT). Nuclear genomes also show a dramatic range of repeat content, suggesting that any sequence can be readily amplified. These two aspects of plant nuclear genomes are well recognized but have rarely been linked. Through investigation of 31 Medicago taxa we detected exceptionally high post-IGT amplification of mitochondrial (mt) DNA sequences containing rps10 in the nuclear genome of Medicago polymorpha and closely related species. The amplified sequences were characterized as tandem arrays of five distinct repeat motifs (2157, 1064, 987, 971, and 587 bp) that have diverged from the mt genome (mitogenome) in the M. polymorpha nuclear genome. The mt rps10-like arrays were identified in seven loci (six intergenic and one telomeric) of the nuclear chromosome assemblies and were the most abundant tandem repeat family, representing 1.6-3.0% of total genomic DNA, a value approximately three-fold greater than the entire mitogenome in M. polymorpha. Compared to a typical mt gene, the mt rps10-like sequence coverage level was 691.5-7198-fold higher in M. polymorpha and closely related species. In addition to the post-IGT amplification, our analysis identified the canonical telomeric repeat and the species-specific satellite arrays that are likely attributable to an ancestral chromosomal fusion in M. polymorpha. A possible relationship between chromosomal instability and the mt rps10-like tandem repeat family in the M. polymorpha clade is discussed.}, } @article {pmid35058355, year = {2022}, author = {Pei, Y and Forstmeier, W and Ruiz-Ruano, FJ and Mueller, JC and Cabrero, J and Camacho, JPM and Alché, JD and Franke, A and Hoeppner, M and Börno, S and Gessara, I and Hertel, M and Teltscher, K and Knief, U and Suh, A and Kempenaers, B}, title = {Occasional paternal inheritance of the germline-restricted chromosome in songbirds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {4}, pages = {}, pmid = {35058355}, issn = {1091-6490}, mesh = {Animals ; *Chromosomes ; Cytogenetic Analysis ; DNA, Mitochondrial ; Evolution, Molecular ; Female ; *Germ Cells ; Haplotypes ; Male ; *Paternal Inheritance ; Phylogeny ; Songbirds/classification/*genetics ; Spermatozoa ; }, abstract = {Songbirds have one special accessory chromosome, the so-called germline-restricted chromosome (GRC), which is only present in germline cells and absent from all somatic tissues. Earlier work on the zebra finch (Taeniopygia guttata castanotis) showed that the GRC is inherited only through the female line-like the mitochondria-and is eliminated from the sperm during spermatogenesis. Here, we show that the GRC has the potential to be paternally inherited. Confocal microscopy using GRC-specific fluorescent in situ hybridization probes indicated that a considerable fraction of sperm heads (1 to 19%) in zebra finch ejaculates still contained the GRC. In line with these cytogenetic data, sequencing of ejaculates revealed that individual males from two families differed strongly and consistently in the number of GRCs in their ejaculates. Examining a captive-bred male hybrid of the two zebra finch subspecies (T. g. guttata and T. g. castanotis) revealed that the mitochondria originated from a castanotis mother, whereas the GRC came from a guttata father. Moreover, analyzing GRC haplotypes across nine castanotis matrilines, estimated to have diverged for up to 250,000 y, showed surprisingly little variability among GRCs. This suggests that a single GRC haplotype has spread relatively recently across all examined matrilines. A few diagnostic GRC mutations that arose since this inferred spreading suggest that the GRC has continued to jump across matriline boundaries. Our findings raise the possibility that certain GRC haplotypes could selfishly spread through the population via occasional paternal transmission, thereby outcompeting other GRC haplotypes that were limited to strict maternal inheritance, even if this was partly detrimental to organismal fitness.}, } @article {pmid35055190, year = {2022}, author = {Belostotsky, R and Frishberg, Y}, title = {Catabolism of Hydroxyproline in Vertebrates: Physiology, Evolution, Genetic Diseases and New siRNA Approach for Treatment.}, journal = {International journal of molecular sciences}, volume = {23}, number = {2}, pages = {}, pmid = {35055190}, issn = {1422-0067}, mesh = {Animals ; Evolution, Molecular ; Genetic Predisposition to Disease ; Glyoxylates/metabolism ; Humans ; Hydrogen Peroxide/metabolism ; Hydroxyproline/*metabolism ; Hyperoxaluria, Primary/drug therapy/*genetics/metabolism ; Mitochondria/metabolism ; Peroxisomes/metabolism ; RNA, Small Interfering/*pharmacology/therapeutic use ; }, abstract = {Hydroxyproline is one of the most prevalent amino acids in animal proteins. It is not a genetically encoded amino acid, but, rather, it is produced by the post-translational modification of proline in collagen, and a few other proteins, by prolyl hydroxylase enzymes. Although this post-translational modification occurs in a limited number of proteins, its biological significance cannot be overestimated. Considering that hydroxyproline cannot be re-incorporated into pro-collagen during translation, it should be catabolized following protein degradation. A cascade of reactions leads to production of two deleterious intermediates: glyoxylate and hydrogen peroxide, which need to be immediately converted. As a result, the enzymes involved in hydroxyproline catabolism are located in specific compartments: mitochondria and peroxisomes. The particular distribution of catabolic enzymes in these compartments, in different species, depends on their dietary habits. Disturbances in hydroxyproline catabolism, due to genetic aberrations, may lead to a severe disease (primary hyperoxaluria), which often impairs kidney function. The basis of this condition is accumulation of glyoxylate and its conversion to oxalate. Since calcium oxalate is insoluble, children with this rare inherited disorder suffer from progressive kidney damage. This condition has been nearly incurable until recently, as significant advances in substrate reduction therapy using small interference RNA led to a breakthrough in primary hyperoxaluria type 1 treatment.}, } @article {pmid35052455, year = {2022}, author = {Deng, MX and Xiao, B and Yuan, JX and Hu, JM and Kim, KS and Westbury, MV and Lai, XL and Sheng, GL}, title = {Ancient Mitogenomes Suggest Stable Mitochondrial Clades of the Siberian Roe Deer.}, journal = {Genes}, volume = {13}, number = {1}, pages = {}, pmid = {35052455}, issn = {2073-4425}, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/analysis/*genetics ; Deer/*genetics ; *Evolution, Molecular ; Fossils ; *Genetic Variation ; *Genome, Mitochondrial ; Haplotypes ; Mitochondria/*genetics ; *Phylogeny ; }, abstract = {The roe deer (Capreolus spp.) has been present in China since the early Pleistocene. Despite abundant fossils available for detailed morphological analyses, little is known about the phylogenetic relationships of the fossil individuals to contemporary roe deer. We generated near-complete mitochondrial genomes for four roe deer remains from Northeastern China to explore the genetic connection of the ancient roe deer to the extant populations and to investigate the evolutionary history and population dynamics of this species. Phylogenetic analyses indicated the four ancient samples fall into three out of four different haplogroups of the Siberian roe deer. Haplogroup C, distributed throughout Eurasia, have existed in Northeastern China since at least the Late Pleistocene, while haplogroup A and D, found in the east of Lake Baikal, emerged in Northeastern China after the Mid Holocene. The Bayesian estimation suggested that the first split within the Siberian roe deer occurred approximately 0.34 million years ago (Ma). Moreover, Bayesian skyline plot analyses suggested that the Siberian roe deer had a population increase between 325 and 225 thousand years ago (Kya) and suffered a transient decline between 50 and 18 Kya. This study provides novel insights into the evolutionary history and population dynamics of the roe deer.}, } @article {pmid35051222, year = {2022}, author = {Tsai, CY and Chiou, SJ and Ko, HJ and Cheng, YF and Lin, SY and Lai, YL and Lin, CY and Wang, C and Cheng, JT and Liu, HF and Kwan, AL and Loh, JK and Hong, YR}, title = {Deciphering the evolution of composite-type GSKIP in mitochondria and Wnt signaling pathways.}, journal = {PloS one}, volume = {17}, number = {1}, pages = {e0262138}, pmid = {35051222}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Armadillo Domain Proteins/chemistry/genetics/*metabolism ; Binding Sites ; Cloning, Molecular ; Conserved Sequence ; Evolution, Molecular ; Glycogen Synthase Kinase 3 beta/*metabolism ; Humans ; Mitochondria/*metabolism ; Models, Molecular ; Mutagenesis, Site-Directed ; Phylogeny ; Protein Binding ; Protein Conformation ; RNA-Binding Proteins/chemistry/genetics/*metabolism ; Repressor Proteins/chemistry/*genetics/*metabolism ; Sequence Analysis, DNA ; Two-Hybrid System Techniques ; Wnt Signaling Pathway ; }, abstract = {We previously revealed the origin of mammalian simple-type glycogen synthase kinase interaction protein (GSKIP), which served as a scavenger and a competitor in the Wnt signaling pathway during evolution. In this study, we investigated the conserved and nonconserved regions of the composite-type GSKIP by utilizing bioinformatics tools, site-directed mutagenesis, and yeast two-hybrid methods. The regions were denoted as the pre-GSK3β binding site, which is located at the front of GSK3β-binding sites. Our data demonstrated that clustered mitochondria protein 1 (CLU1), a type of composite-type GSKIP that exists in the mitochondria of all eukaryotic organisms, possesses the protein known as domain of unknown function 727 (DUF727), with a pre-GSK3β-binding site and a mutant GSK3β-binding flanking region. Another type of composite-type GSKIP, armadillo repeat containing 4 (ARMC4), which is known for cilium movement in vertebrates, contains an unintegrated DUF727 flanking region with a pre-GSK3β-binding site (115SPxF118) only. In addition, the sequence of the GSK3β-binding site in CLU1 revealed that Q126L and V130L were not conserved, differing from the ideal GSK3β-binding sequence of simple-type GSKIP. We further illustrated two exceptions, namely 70 kilodalton heat shock proteins (Hsp70/DnaK) and Mitofilin in nematodes, that presented an unexpected ideal GSK3β-binding region with a pre-GSK3β sequence; this composite-type GSKIP could only occur in vertebrate species. Furthermore, we revealed the importance of the pre-GSK3β-binding site (118F or 118Y) and various mutant GSK3β-binding sites of composite-type GSKIP. Collectively, our data suggest that the new composite-type GSKIP starts with a DUF727 domain followed by a pre-GSK3β-binding site, with the subsequent addition of the GSK3β-binding site, which plays vital roles for CLU1, Mitofilin, and ARMC4 in mitochondria and Wnt signaling pathways during evolution.}, } @article {pmid35039544, year = {2022}, author = {Lebedev, VS and Shenbrot, GI and Krystufek, B and Mahmoudi, A and Melnikova, MN and Solovyeva, EN and Lisenkova, AA and Undrakhbayar, E and Rogovin, KA and Surov, AV and Bannikova, AA}, title = {Phylogenetic relations and range history of jerboas of the Allactaginae subfamily (Dipodidae, Rodentia).}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {842}, pmid = {35039544}, issn = {2045-2322}, mesh = {Animals ; Ecosystem ; European Union ; Genetic Variation ; Mitochondria/genetics ; *Phylogeny ; Rodentia/classification/*genetics ; Species Specificity ; }, abstract = {Five-toed jerboas of the subfamily Allactaginae comprise several complex taxa occurring over a wide distribution range covering a large part of the Eurasian arid belt. In this study, we employed current methods of molecular phylogenetics based on 15 nuclear genes and the mitochondrial gene cytb to revise relations and systematics within Allactaginae. We also applied species distribution modelling projected on paleo-environmental data to reconstruct the geographic patterns of speciation in Allactaginae. We elucidated the intergeneric relationships within this subfamily and clarified interspecies relations within the genus Scarturus. Moreover, our results demonstrate the species status of S. caprimulga; outline the currently understudied diversity within Orientallactaga, Allactaga, and Pygeretmus; and improve the divergence estimates of these taxa. Based on our results from modelling of geographic range fragmentation in allactagines, we suggest the dating and location of speciation events and present hypotheses regarding general habitat niche conservatism in small mammals.}, } @article {pmid35038074, year = {2022}, author = {Zhang, H and Qin, J and Lan, X and Zeng, W and Zhou, J and Huang, TE and Xiao, WL and Wang, QQ and Sun, S and Su, W and Nie, W and Yang, S and Yang, J and Gao, Q and Xiang, Y}, title = {Handelin extends lifespan and healthspan of Caenorhabditis elegans by reducing ROS generation and improving motor function.}, journal = {Biogerontology}, volume = {23}, number = {1}, pages = {115-128}, pmid = {35038074}, issn = {1573-6768}, mesh = {Animals ; *Caenorhabditis elegans/physiology ; *Caenorhabditis elegans Proteins/genetics/metabolism ; Ethanol/pharmacology ; Longevity/physiology ; Mammals/metabolism ; Plant Extracts/pharmacology ; Reactive Oxygen Species/metabolism ; Terpenes ; }, abstract = {Aging and aging-related disorders contribute to formidable socioeconomic and healthcare challenges. Several promising small molecules have been identified to target conserved genetic pathways delaying aging to extend lifespan and healthspan in many organisms. We previously found that extract from an edible and medicinal plant Chrysanthemum indicum L. (C. indicum L.) protect skin from UVB-induced photoaging, partially by reducing reactive oxygen species (ROS) generation. Thus, we hypothesized that C. indicum L. and its biological active compound may extend lifespan and health span in vivo. We find that both water and ethanol extracts from C. indicum L. extended lifespan of Caenorhabditis elegans, with better biological effect on life extending for ethanol extracts. As one of the major biological active compounds, handelin extended lifespan of C. elegans too. RNA-seq analysis revealed overall gene expression change of C. elegans post stimulation of handelin focus on several antioxidative proteins. Handelin significantly reduced ROS level and maintained the number and morphology of mitochondria. Moreover, handelin improveed many C. elegans behaviors related to healthspan, including increased pharyngeal pumping and body movement. Muscle fiber imaging analyses revealed that handelin maintains muscle architecture by stabilizing myofilaments. In conclusion, our present study finds a novel compound handelin, from C. indicum L., which bring about biologically beneficial effects by mild stress response, termed as hormetin, that can extend both lifespan and healthspan in vivo on C. elegans. Further study on mammal animal model of natural aging or sarcopenia will verify the potential clinical value of handelin.}, } @article {pmid35027725, year = {2022}, author = {Muñoz-Gómez, SA and Susko, E and Williamson, K and Eme, L and Slamovits, CH and Moreira, D and López-García, P and Roger, AJ}, title = {Site-and-branch-heterogeneous analyses of an expanded dataset favour mitochondria as sister to known Alphaproteobacteria.}, journal = {Nature ecology & evolution}, volume = {6}, number = {3}, pages = {253-262}, pmid = {35027725}, issn = {2397-334X}, mesh = {*Alphaproteobacteria/genetics/metabolism ; Metagenome ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins ; Phylogeny ; }, abstract = {Determining the phylogenetic origin of mitochondria is key to understanding the ancestral mitochondrial symbiosis and its role in eukaryogenesis. However, the precise evolutionary relationship between mitochondria and their closest bacterial relatives remains hotly debated. The reasons include pervasive phylogenetic artefacts as well as limited protein and taxon sampling. Here we developed a new model of protein evolution that accommodates both across-site and across-branch compositional heterogeneity. We applied this site-and-branch-heterogeneous model (MAM60 + GFmix) to a considerably expanded dataset that comprises 108 mitochondrial proteins of alphaproteobacterial origin, and novel metagenome-assembled genomes from microbial mats, microbialites and sediments. The MAM60 + GFmix model fits the data much better and agrees with analyses of compositionally homogenized datasets with conventional site-heterogenous models. The consilience of evidence thus suggests that mitochondria are sister to the Alphaproteobacteria to the exclusion of MarineProteo1 and Magnetococcia. We also show that the ancestral presence of the crista-developing mitochondrial contact site and cristae organizing system (a mitofilin-domain-containing Mic60 protein) in mitochondria and the Alphaproteobacteria only supports their close relationship.}, } @article {pmid35026224, year = {2022}, author = {Uzarska, MA and Grochowina, I and Soldek, J and Jelen, M and Schilke, B and Marszalek, J and Craig, EA and Dutkiewicz, R}, title = {During FeS cluster biogenesis, ferredoxin and frataxin use overlapping binding sites on yeast cysteine desulfurase Nfs1.}, journal = {The Journal of biological chemistry}, volume = {298}, number = {2}, pages = {101570}, pmid = {35026224}, issn = {1083-351X}, support = {R35 GM127009/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; Carbon-Sulfur Lyases/genetics/metabolism ; *Ferredoxins/metabolism ; Iron-Binding Proteins/metabolism ; *Iron-Sulfur Proteins/metabolism ; *Mitochondrial Proteins/metabolism ; Saccharomyces cerevisiae/enzymology/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/metabolism ; *Sulfurtransferases/metabolism ; }, abstract = {In mitochondria, cysteine desulfurase (Nfs1) plays a central role in the biosynthesis of iron-sulfur (FeS) clusters, cofactors critical for activity of many cellular proteins. Nfs1 functions both as a sulfur donor for cluster assembly and as a binding platform for other proteins functioning in the process. These include not only the dedicated scaffold protein (Isu1) on which FeS clusters are synthesized but also accessory FeS cluster biogenesis proteins frataxin (Yfh1) and ferredoxin (Yah1). Yfh1 has been shown to activate cysteine desulfurase enzymatic activity, whereas Yah1 supplies electrons for the persulfide reduction. While Yfh1 interaction with Nfs1 is well understood, the Yah1-Nfs1 interaction is not. Here, based on the results of biochemical experiments involving purified WT and variant proteins, we report that in Saccharomyces cerevisiae, Yah1 and Yfh1 share an evolutionary conserved interaction site on Nfs1. Consistent with this notion, Yah1 and Yfh1 can each displace the other from Nfs1 but are inefficient competitors when a variant with an altered interaction site is used. Thus, the binding mode of Yah1 and Yfh1 interacting with Nfs1 in mitochondria of S. cerevisiae resembles the mutually exclusive binding of ferredoxin and frataxin with cysteine desulfurase reported for the bacterial FeS cluster assembly system. Our findings are consistent with the generally accepted scenario that the mitochondrial FeS cluster assembly system was inherited from bacterial ancestors of mitochondria.}, } @article {pmid35025030, year = {2022}, author = {Liu, S and Liu, Y and He, J and Lin, Z and Xue, Q}, title = {The complete mitochondrial genome of Crassostrea hongkongensis from East China Sea indicates species' range may extend northward.}, journal = {Molecular biology reports}, volume = {49}, number = {2}, pages = {1631-1635}, pmid = {35025030}, issn = {1573-4978}, mesh = {Animals ; China ; Conservation of Natural Resources/methods ; Crassostrea/*genetics ; Ecosystem ; Genome, Mitochondrial/*genetics ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Crassostrea hongkongensis is an important mariculture shellfish with a relatively narrow distribution range. Recently, larger wild oysters were identified as C. hongkongensis from Sanmen bay in East China Sea. No natural distribution had been reported for this species here, and its origin remains unknown.

METHODS AND RESULTS: We assembled the complete 18,617 bp circular mitochondrial genome of C. hongkongensis from Sanmen bay by next generation sequencing. It included 12 protein-coding genes, 23 tRNAs, and two rRNAs. The A/T content of the mitogenome was higher than its G/C content. Similar values and features were previously found for five other specimens of C. hongkongensis, and were comparable to those of other congeneric species. A phylogenetic analysis based on the 12 protein-coding genes and complete mitochondrial sequence indicated that the six specimens of C. hongkongensis formed a monophyletic group and shared a sister group relationship with C. ariakensis, C. nippona, C. sikamea, C. angulata, C. gigas, and C. iredalei, whereas specimens from the Sanmen bay area clustered later with the five other C. hongkongensis individuals, sharing a sub-clade. The newly sequenced mitogenome had more singleton sites than previously published C. hongkongensis mitogenomes.

CONCLUSIONS: Crassostrea hongkongensis may be a native species, and the species' range extends further to the north than previously known. Our data may therefore contribute to a better understanding of the species diversity and conservation of Crassostrea oysters.}, } @article {pmid35022483, year = {2022}, author = {Dash, A and Ghag, SB}, title = {Genome-wide in silico characterization and stress induced expression analysis of BcL-2 associated athanogene (BAG) family in Musa spp.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {625}, pmid = {35022483}, issn = {2045-2322}, mesh = {*Phylogeny ; }, abstract = {Programmed cell death (PCD) is a genetically controlled process for the selective removal of damaged cells. Though understanding about plant PCD has improved over years, the mechanisms are yet to be fully deciphered. Among the several molecular players of PCD in plants, B cell lymphoma 2 (Bcl-2)-associated athanogene (BAG) family of co-chaperones are evolutionary conserved and regulate cell death, growth and development. In this study, we performed a genome-wide in silico analysis of the MusaBAG gene family in a globally important fruit crop banana. Thirteen MusaBAG genes were identified, out of which MusaBAG1, 7 and 8 genes were found to have multiple copies. MusaBAG genes were distributed on seven out of 11 chromosomes in banana. Except for one paralog of MusaBAG8 all the other 12 proteins have characteristic BAG domain. MusaBAG1, 2 and 4 have an additional ubiquitin-like domain whereas MusaBAG5-8 have a calmodulin binding motif. Most of the MusaBAG proteins were predicted to be localized in the nucleus and mitochondria or chloroplast. The in silico cis-regulatory element analysis suggested regulation associated with photoperiodic control, abiotic and biotic stress. The phylogenetic analysis revealed 2 major clusters. Digital gene expression analysis and quantitative real-time RT-PCR depicted the differential expression pattern of MusaBAG genes under abiotic and biotic stress conditions. Further studies are warranted to uncover the role of each of these proteins in growth, PCD and stress responses so as to explore them as candidate genes for engineering transgenic banana plants with improved agronomic traits.}, } @article {pmid35020439, year = {2022}, author = {Gogoi, J and Bhatnagar, A and Ann, KJ and Pottabathini, S and Singh, R and Mazeed, M and Kuncha, SK and Kruparani, SP and Sankaranarayanan, R}, title = {Switching a conflicted bacterial DTD-tRNA code is essential for the emergence of mitochondria.}, journal = {Science advances}, volume = {8}, number = {2}, pages = {eabj7307}, pmid = {35020439}, issn = {2375-2548}, abstract = {Mitochondria emerged through an endosymbiotic event involving a proteobacterium and an archaeal host. However, the process of optimization of cellular processes required for the successful evolution and survival of mitochondria, which integrates components from two evolutionarily distinct ancestors as well as novel eukaryotic elements, is not well understood. We identify two key switches in the translational machinery—one in the discriminator recognition code of a chiral proofreader DTD [d-aminoacyl–transfer RNA (tRNA) deacylase] and the other in mitochondrial tRNA[Gly]—that enable the compatibility between disparate elements essential for survival. Notably, the mito-tRNA[Gly] discriminator element is the only one to switch from pyrimidine to purine during the bacteria-to-mitochondria transition. We capture this code transition in the Jakobida, an early diverging eukaryotic clade bearing the most bacterial-like mito-genome, wherein both discriminator elements are present. This study underscores the need to explore the fundamental integration strategies critical for mitochondrial and eukaryotic evolution.}, } @article {pmid35017538, year = {2022}, author = {Li, CH and Haider, S and Boutros, PC}, title = {Age influences on the molecular presentation of tumours.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {208}, pmid = {35017538}, issn = {2041-1723}, support = {P30 CA016042/CA/NCI NIH HHS/United States ; U01 CA214194/CA/NCI NIH HHS/United States ; SVB-145586//CIHR/Canada ; }, mesh = {Age Factors ; Aging/*genetics/metabolism ; CREB-Binding Protein/*genetics/metabolism ; Carcinogenesis/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism ; *DNA Repair ; DNA, Neoplasm/*genetics/metabolism ; Datasets as Topic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mitochondria/metabolism ; Mutation Rate ; Neoplasm Proteins/*genetics/metabolism ; Neoplasms/classification/*genetics/metabolism/pathology ; Repressor Proteins/deficiency/genetics ; Smoking/genetics/metabolism ; Transcriptome ; X-linked Nuclear Protein/genetics/metabolism ; }, abstract = {Cancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterise them, we analyse age-associations in the nuclear and mitochondrial somatic mutational landscape of 20,033 tumours across 35 tumour-types. Age influences both the number of mutations in a tumour (0.077 mutations per megabase per year) and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes such as a greater influence of tobacco use in the tumours of younger patients, but higher activity of DNA damage repair signatures in those of older patients. We find that known cancer driver genes such as CDKN2A and CREBBP are mutated in age-associated frequencies, and these alter the transcriptome and predict for clinical outcomes. These effects are most striking in brain cancers where alterations like SUFU loss and ATRX mutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.}, } @article {pmid35007655, year = {2022}, author = {Liu, T and Lin, S and Du, Y and Gong, Y and Li, S}, title = {SpBAG3 assisted WSSV infection in mud crab (Scylla paramamosain) by inhibiting apoptosis.}, journal = {Developmental and comparative immunology}, volume = {129}, number = {}, pages = {104349}, doi = {10.1016/j.dci.2022.104349}, pmid = {35007655}, issn = {1879-0089}, mesh = {Animals ; Apoptosis ; Apoptosis Regulatory Proteins/genetics ; Arthropod Proteins/genetics ; Brachyura/*immunology ; Gene Expression Profiling ; Hemocytes/immunology ; Immunity, Innate/genetics ; Membrane Potential, Mitochondrial ; Mitochondria/metabolism ; Phylogeny ; White spot syndrome virus 1/physiology ; }, abstract = {The function of B-cell lymphoma-2 (Bcl-2) family proteins can be divided into two categories: anti-apoptotic and pro-apoptotic. As an anti-apoptotic protein, Bcl2-associated athanogene 3 (BAG3) plays a key role in regulating apoptosis, development, cell movement, and autophagy, and mediating the adaptability of cells to stimulation. However, SpBAG3 has not been reported in mud crab (Scylla paramamosain), and the regulatory effect of SpBAG3 on apoptosis in mud crab and its function in antiviral immunity is still unknown. In this study, SpBAG3 was found, and characterized, which encoded a total of 175 amino acid (molecular mass 19.3 kDa), including a specific conserved domain of the BAG family. SpBAG3 was significantly down-regulated at 0-48 h post-infection with WSSV in vivo. The antiviral effect of SpBAG3 was investigated using RNA interference. The results indicated that SpBAG3 might be involved in assisting the replication of WSSV in the host. SpBAG3 could change the mitochondrial membrane potential (△ψm), and affect cell apoptosis through mitochondrial apoptotic pathways. Therefore, the results of this study suggested that SpBAG3 could assist WSSV infection by inhibiting the apoptosis of the hemocytes in mud crab.}, } @article {pmid34997986, year = {2022}, author = {Ereskovsky, A and Tokina, D}, title = {Ultrastructural research of spermiogenesis in two sponges, Crellomima imparidens and Hymedesmia irregularis (Demospongiae): New evidence of sperms with acrosome in sponges.}, journal = {Journal of morphology}, volume = {283}, number = {3}, pages = {333-345}, doi = {10.1002/jmor.21446}, pmid = {34997986}, issn = {1097-4687}, mesh = {*Acrosome/ultrastructure ; Animals ; Male ; Phylogeny ; *Porifera ; Spermatids/ultrastructure ; Spermatogenesis ; Spermatozoa ; }, abstract = {Details of spermatogenesis and sperm organization are often useful for reconstructing the phylogeny of closely related taxa of invertebrates. Here, the spermiogenesis and the ultrastructure of sperm were studied in two marine demosponges, Crellomima imparidens and Hymedesmia irregularis (order Poecilosclerida). In C. imparidens and H. irregularis, we found bundles of microtubules arranged along the nucleus during spermiogenesis. These bundles derived from the basal body of axoneme, reaching the apical pole of the cell. In C. imparidens, the microtubules surround the nucleus, forming the manchette. In H. irregularis, the microtubules pass along only one side of the cell periphery. During spermiogenesis, the nucleus stretches and elongates. In both species, the nucleus is twisted into a spiral structure. We suppose that the manchette of microtubules could be responsible for controlling the elongation and shaping of the sperm nucleus to a helical form and for the twisting and/or condensation of chromatin in these sponges. The spermatozoon of both species has an elongated shape. Its apical part has an acrosome, which is dome-shaped in C. imparidens and flattened and lenticular in H. irregularis. The cytoplasm of the spermatozoa contains some small mitochondria, and proximal and distal centrioles arranged at an angle to each other. There is a small volume of residual cytoplasm with dark glycogen-like granules. The axoneme of the spermatid and the flagellum of the sperm of both sponges is located in the deep tunnel-like cytoplasmic depression. The comparison of spermatozoa morphology of different species of the order Poecilosclerida demonstrates that the knowledge of variation within genera and families can give valuable insights into the significance of many characters proposed for phylogenetic studies of this order.}, } @article {pmid34994554, year = {2022}, author = {Liu, Y and Li, Q and Gu, M and Lu, D and Xiong, X and Zhang, Z and Pan, Y and Liao, Y and Ding, Q and Gong, W and Chen, DS and Guan, M and Wu, J and Tian, Z and Deng, H and Gu, L and Hong, X and Xiao, Y}, title = {A Second Near-Infrared Ru(II) Polypyridyl Complex for Synergistic Chemo-Photothermal Therapy.}, journal = {Journal of medicinal chemistry}, volume = {65}, number = {3}, pages = {2225-2237}, doi = {10.1021/acs.jmedchem.1c01736}, pmid = {34994554}, issn = {1520-4804}, mesh = {Apoptosis/drug effects ; Biocompatible Materials/chemistry/pharmacology/therapeutic use ; Cell Line, Tumor ; Coordination Complexes/*chemistry/pharmacology/therapeutic use ; Drug Design ; Fluorescent Dyes/chemistry/pharmacology/therapeutic use ; G2 Phase Cell Cycle Checkpoints/drug effects ; Humans ; Hyperthermia, Induced ; *Infrared Rays ; Neoplasms/diagnostic imaging/drug therapy/therapy ; Phenazines/chemistry ; Photothermal Therapy/methods ; Polyethylene Glycols/chemistry ; Quantum Theory ; Ruthenium/*chemistry ; Spectroscopy, Near-Infrared ; }, abstract = {The clinical success of cisplatin ushered in a new era of the application of metallodrugs. When it comes to practice, however, drug resistance, tumor recurrence, and drug systemic toxicity make it implausible to completely heal the patients. Herein, we successfully transform an electron acceptor [1, 2, 5]thiadiazolo[3,4-g]quinoxaline into a novel second near-infrared (NIR-II) fluorophore H7. After PEGylation and chelation, HL-PEG2k exhibits a wavelength bathochromic shift, enhanced photothermal conversion efficiency (41.77%), and an antineoplastic effect against glioma. Its potential for in vivo tumor tracking and image-guided chemo-photothermal therapy is explored. High levels of uptake and high-resolution NIR-II imaging results are thereafter obtained. The hyperthermia effect could disrupt the lysosomal membranes, which in turn aggravate the mitochondria dysfunction, arrest the cell cycle in the G2 phase, and finally lead to cancer cell apoptosis. HL-PEG2k displays a superior biocompatibility and thus can be a potential theranostic platform to combat the growth and recurrence of tumors.}, } @article {pmid34993838, year = {2022}, author = {Jiang, Z and Cai, X and Kong, J and Zhang, R and Ding, Y}, title = {Maternally transmitted diabetes mellitus may be associated with mitochondrial ND5 T12338C and tRNA[Ala] T5587C variants.}, journal = {Irish journal of medical science}, volume = {191}, number = {6}, pages = {2625-2633}, pmid = {34993838}, issn = {1863-4362}, mesh = {Humans ; *RNA, Transfer, Ala ; *Diabetes Mellitus, Type 2/genetics ; Phylogeny ; DNA, Mitochondrial/genetics ; Mitochondria ; Pedigree ; Mutation ; }, abstract = {INTRODUCTION: Mutations/variants in mitochondrial genomes are found to be associated with type 2 diabetes mellitus (T2DM), but the pathophysiology of this disease remains largely unknown.

AIM: The aim of this study is to investigate the relationship between mitochondrial DNA (mtDNA) variants and T2DM.

METHODOLOGY: A maternally inherited T2DM pedigree is underwent clinical, genetic, and molecular assessment. Moreover, the complete mitochondrial genomes of the matrilineal relatives of this family are PCR amplified and sequenced. We also utilize the phylogenetic conservation analysis, haplogroup classification, and the pathogenicity scoring system to determine the T2DM-associated potential pathogenic mtDNA variants.

RESULT: Four of seven matrilineal relatives of this pedigree suffered from T2DM with variable ages of onset. Screening for the entire mtDNA genes of matrilineal members reveals co-existence of ND5 T12338C and tRNA[Ala] T5587C variants, as well as 21 genetic polymorphisms which belong to East Asian haplogroup F2. Interestingly, the T12338C variant causes the alternation of first amino acid Met to Thr, shortened two amino acids of ND5 protein. Furthermore, T5587C variant is located at position 73 in the 3'end of mt-tRNA[Ala] and may have structural and functional consequences.

CONCLUSIONS: The co-occurrence of ND5 T12338C and tRNA[Ala] T5587C variants may impair the mitochondrial function, which are associated with the development of T2DM in this family.}, } @article {pmid34976854, year = {2021}, author = {Valdés-Aguayo, JJ and Garza-Veloz, I and Vargas-Rodríguez, JR and Martinez-Vazquez, MC and Avila-Carrasco, L and Bernal-Silva, S and González-Fuentes, C and Comas-García, A and Alvarado-Hernández, DE and Centeno-Ramirez, ASH and Rodriguez-Sánchez, IP and Delgado-Enciso, I and Martinez-Fierro, ML}, title = {Peripheral Blood Mitochondrial DNA Levels Were Modulated by SARS-CoV-2 Infection Severity and Its Lessening Was Associated With Mortality Among Hospitalized Patients With COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {754708}, pmid = {34976854}, issn = {2235-2988}, mesh = {*COVID-19 ; DNA, Mitochondrial/genetics ; Humans ; Immunity, Innate ; Mitochondria/genetics ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus hijacks the mitochondria causing damage of its membrane and release of mt-DNA into the circulation which can trigger innate immunity and generate an inflammatory state. In this study, we explored the importance of peripheral blood mt-DNA as an early predictor of evolution in patients with COVID-19 and to evaluate the association between the concentration of mt-DNA and the severity of the disease and the patient's outcome.

METHODS: A total 102 patients (51 COVID-19 cases and 51 controls) were included in the study. mt-DNA obtained from peripheral blood was quantified by qRT-PCR using the NADH mitochondrial gene.

RESULTS: There were differences in peripheral blood mt-DNA between patients with COVID-19 (4.25 ng/μl ± 0.30) and controls (3.3 ng/μl ± 0.16) (p = 0.007). Lower mt-DNA concentrations were observed in patients with severe COVID-19 when compared with mild (p= 0.005) and moderate (p= 0.011) cases of COVID-19. In comparison with patients with severe COVID-19 who survived (3.74 ± 0.26 ng/μl) decreased levels of mt-DNA in patients with severe COVID-19 who died (2.4 ± 0.65 ng/μl) were also observed (p = 0.037).

CONCLUSION: High levels of mt-DNA were associated with COVID-19 and its decrease could be used as a potential biomarker to establish a prognosis of severity and mortality of patients with COVID-19.}, } @article {pmid34972821, year = {2022}, author = {Irwin, NAT and Pittis, AA and Richards, TA and Keeling, PJ}, title = {Systematic evaluation of horizontal gene transfer between eukaryotes and viruses.}, journal = {Nature microbiology}, volume = {7}, number = {2}, pages = {327-336}, pmid = {34972821}, issn = {2058-5276}, mesh = {Eukaryota/*genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; *Host Microbial Interactions ; Phylogeny ; Viruses/*genetics ; }, abstract = {Gene exchange between viruses and their hosts acts as a key facilitator of horizontal gene transfer and is hypothesized to be a major driver of evolutionary change. Our understanding of this process comes primarily from bacteria and phage co-evolution, but the mode and functional importance of gene transfers between eukaryotes and their viruses remain anecdotal. Here we systematically characterized viral-eukaryotic gene exchange across eukaryotic and viral diversity, identifying thousands of transfers and revealing their frequency, taxonomic distribution and projected functions. Eukaryote-derived viral genes, abundant in the Nucleocytoviricota, highlighted common strategies for viral host-manipulation, including metabolic reprogramming, proteolytic degradation and extracellular modification. Furthermore, viral-derived eukaryotic genes implicate genetic exchange in the early evolution and diversification of eukaryotes, particularly through viral-derived glycosyltransferases, which have impacted structures as diverse as algal cell walls, trypanosome mitochondria and animal tissues. These findings illuminate the nature of viral-eukaryotic gene exchange and its impact on the evolution of viruses and their eukaryotic hosts.}, } @article {pmid34964900, year = {2022}, author = {Rand, DM and Mossman, JA and Spierer, AN and Santiago, JA}, title = {Mitochondria as environments for the nuclear genome in Drosophila: mitonuclear G×G×E.}, journal = {The Journal of heredity}, volume = {113}, number = {1}, pages = {37-47}, pmid = {34964900}, issn = {1465-7333}, support = {R01 GM067862/GM/NIGMS NIH HHS/United States ; R35 GM139607/GM/NIGMS NIH HHS/United States ; 1R35GM139607/NH/NIH HHS/United States ; 2R01GM067862/NH/NIH HHS/United States ; }, mesh = {Animals ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; *Drosophila/genetics ; Epistasis, Genetic ; *Genome, Mitochondrial ; Mitochondria/genetics ; }, abstract = {Mitochondria evolved from a union of microbial cells belonging to distinct lineages that were likely anaerobic. The evolution of eukaryotes required a massive reorganization of the 2 genomes and eventual adaptation to aerobic environments. The nutrients and oxygen that sustain eukaryotic metabolism today are processed in mitochondria through coordinated expression of 37 mitochondrial genes and over 1000 nuclear genes. This puts mitochondria at the nexus of gene-by-gene (G×G) and gene-by-environment (G×E) interactions that sustain life. Here we use a Drosophila model of mitonuclear genetic interactions to explore the notion that mitochondria are environments for the nuclear genome, and vice versa. We construct factorial combinations of mtDNA and nuclear chromosomes to test for epistatic interactions (G×G), and expose these mitonuclear genotypes to altered dietary environments to examine G×E interactions. We use development time and genome-wide RNAseq analyses to assess the relative contributions of mtDNA, nuclear chromosomes, and environmental effects on these traits (mitonuclear G×G×E). We show that the nuclear transcriptional response to alternative mitochondrial "environments" (G×G) has significant overlap with the transcriptional response of mitonuclear genotypes to altered dietary environments. These analyses point to specific transcription factors (e.g., giant) that mediated these interactions, and identified coexpressed modules of genes that may account for the overlap in differentially expressed genes. Roughly 20% of the transcriptome includes G×G genes that are concordant with G×E genes, suggesting that mitonuclear interactions are part of an organism's environment.}, } @article {pmid34946978, year = {2021}, author = {Romanova, EV and Bukin, YS and Mikhailov, KV and Logacheva, MD and Aleoshin, VV and Sherbakov, DY}, title = {The Mitochondrial Genome of a Freshwater Pelagic Amphipod Macrohectopus branickii Is among the Longest in Metazoa.}, journal = {Genes}, volume = {12}, number = {12}, pages = {}, pmid = {34946978}, issn = {2073-4425}, mesh = {Amphipoda/*genetics ; Animals ; Gene Order ; Genes, rRNA ; Genome Size ; Genome, Mitochondrial ; Mitochondria/*genetics ; RNA, Transfer/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {There are more than 350 species of amphipods (Crustacea) in Lake Baikal, which have emerged predominantly through the course of endemic radiation. This group represents a remarkable model for studying various aspects of evolution, one of which is the evolution of mitochondrial (mt) genome architectures. We sequenced and assembled the mt genome of a pelagic Baikalian amphipod species Macrohectopus branickii. The mt genome is revealed to have an extraordinary length (42,256 bp), deviating significantly from the genomes of other amphipod species and the majority of animals. The mt genome of M. branickii has a unique gene order within amphipods, duplications of the four tRNA genes and Cox2, and a long non-coding region, that makes up about two thirds of the genome's size. The extension of the mt genome was most likely caused by multiple duplications and inversions of regions harboring ribosomal RNA genes. In this study, we analyzed the patterns of mt genome length changes in amphipods and other animal phyla. Through a statistical analysis, we demonstrated that the variability in the mt genome length may be a characteristic of certain phyla and is primarily conferred by expansions of non-coding regions.}, } @article {pmid34946956, year = {2021}, author = {Tahami, MS and Dincă, V and Lee, KM and Vila, R and Joshi, M and Heikkilä, M and Dapporto, L and Schmid, S and Huemer, P and Mutanen, M}, title = {Genomics Reveal Admixture and Unexpected Patterns of Diversity in a Parapatric Pair of Butterflies.}, journal = {Genes}, volume = {12}, number = {12}, pages = {}, pmid = {34946956}, issn = {2073-4425}, mesh = {Animals ; Balkan Peninsula ; Butterflies/anatomy & histology/*classification/genetics ; Cell Nucleus/*genetics ; DNA, Mitochondrial/*genetics ; Evolution, Molecular ; Gene Flow ; Genetic Speciation ; Genomics/*methods ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA ; Sympatry ; }, abstract = {We studied the evolutionary relationship of two widely distributed parapatric butterfly species, Melitaea athalia and Melitaea celadussa, using the ddRAD sequencing approach, as well as genital morphology and mtDNA data. M. athalia was retrieved as paraphyletic with respect to M. celadussa. Several cases of mito-nuclear discordance and morpho-genetic mismatch were found in the contact zone. A strongly diverged and marginally sympatric clade of M. athalia from the Balkans was revealed. An in-depth analysis of genomic structure detected high levels of admixture between M. athalia and M. celadussa at the contact zone, though not reaching the Balkan clade. The demographic modelling of populations supported the intermediate genetic make-up of European M. athalia populations with regards to M. celadussa and the Balkan clade. However, the dissimilarity matrix of genotype data (PCoA) suggested the Balkan lineage having a genetic component that is unrelated to the athalia-celadussa group. Although narrowly sympatric, almost no signs of gene flow were found between the main M. athalia group and the Balkan clade. We propose two possible scenarios on the historical evolution of our model taxa and the role of the last glacial maximum in shaping their current distribution. Finally, we discuss the complexities regarding the taxonomic delimitation of parapatric taxa.}, } @article {pmid34943968, year = {2021}, author = {Singh, LN and Kao, SH and Wallace, DC}, title = {Unlocking the Complexity of Mitochondrial DNA: A Key to Understanding Neurodegenerative Disease Caused by Injury.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34943968}, issn = {2073-4409}, support = {MH108592/NH/NIH HHS/United States ; P50 HD105354/HD/NICHD NIH HHS/United States ; OD010944/NH/NIH HHS/United States ; NS021328/NH/NIH HHS/United States ; }, mesh = {Brain Injuries, Traumatic/*genetics/pathology ; DNA, Mitochondrial/*genetics ; Genetic Variation/genetics ; Humans ; Mitochondria/*genetics ; Risk Factors ; Stroke/*genetics/pathology ; }, abstract = {Neurodegenerative disorders that are triggered by injury typically have variable and unpredictable outcomes due to the complex and multifactorial cascade of events following the injury and during recovery. Hence, several factors beyond the initial injury likely contribute to the disease progression and pathology, and among these are genetic factors. Genetics is a recognized factor in determining the outcome of common neurodegenerative diseases. The role of mitochondrial genetics and function in traditional neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, is well-established. Much less is known about mitochondrial genetics, however, regarding neurodegenerative diseases that result from injuries such as traumatic brain injury and ischaemic stroke. We discuss the potential role of mitochondrial DNA genetics in the progression and outcome of injury-related neurodegenerative diseases. We present a guide for understanding mitochondrial genetic variation, along with the nuances of quantifying mitochondrial DNA variation. Evidence supporting a role for mitochondrial DNA as a risk factor for neurodegenerative disease is also reviewed and examined. Further research into the impact of mitochondrial DNA on neurodegenerative disease resulting from injury will likely offer key insights into the genetic factors that determine the outcome of these diseases together with potential targets for treatment.}, } @article {pmid34943861, year = {2021}, author = {Key, J and Torres-Odio, S and Bach, NC and Gispert, S and Koepf, G and Reichlmeir, M and West, AP and Prokisch, H and Freisinger, P and Newman, WG and Shalev, S and Sieber, SA and Wittig, I and Auburger, G}, title = {Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34943861}, issn = {2073-4409}, support = {R01 HL148153/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Amino Acids/metabolism ; Brain/metabolism ; Cell Nucleus/*metabolism ; Computational Biology ; Conserved Sequence ; DNA, Mitochondrial/*metabolism ; Endopeptidase Clp/*metabolism ; Fibroblasts/metabolism ; Humans ; Male ; Mitochondria/*metabolism ; Mitochondrial Proteins/metabolism ; Models, Biological ; Protein Binding ; Protein Interaction Maps ; Proteome/metabolism ; Skin/pathology ; Subcellular Fractions/metabolism ; Transcription, Genetic ; }, abstract = {Biallelic pathogenic variants in CLPP, encoding mitochondrial matrix peptidase ClpP, cause a rare autosomal recessive condition, Perrault syndrome type 3 (PRLTS3). It is characterized by primary ovarian insufficiency and early sensorineural hearing loss, often associated with progressive neurological deficits. Mouse models showed that accumulations of (i) its main protein interactor, the substrate-selecting AAA+ ATPase ClpX, (ii) mitoribosomes, and (iii) mtDNA nucleoids are the main cellular consequences of ClpP absence. However, the sequence of these events and their validity in human remain unclear. Here, we studied global proteome profiles to define ClpP substrates among mitochondrial ClpX interactors, which accumulated consistently in ClpP-null mouse embryonal fibroblasts and brains. Validation work included novel ClpP-mutant patient fibroblast proteomics. ClpX co-accumulated in mitochondria with the nucleoid component POLDIP2, the mitochondrial poly(A) mRNA granule element LRPPRC, and tRNA processing factor GFM1 (in mouse, also GRSF1). Only in mouse did accumulated ClpX, GFM1, and GRSF1 appear in nuclear fractions. Mitoribosomal accumulation was minor. Consistent accumulations in murine and human fibroblasts also affected multimerizing factors not known as ClpX interactors, namely, OAT, ASS1, ACADVL, STOM, PRDX3, PC, MUT, ALDH2, PMPCB, UQCRC2, and ACADSB, but the impact on downstream metabolites was marginal. Our data demonstrate the primary impact of ClpXP on the assembly of proteins with nucleic acids and show nucleoid enlargement in human as a key consequence.}, } @article {pmid34942301, year = {2022}, author = {Bohálová, N and Dobrovolná, M and Brázda, V and Bidula, S}, title = {Conservation and over-representation of G-quadruplex sequences in regulatory regions of mitochondrial DNA across distinct taxonomic sub-groups.}, journal = {Biochimie}, volume = {194}, number = {}, pages = {28-34}, doi = {10.1016/j.biochi.2021.12.006}, pmid = {34942301}, issn = {1638-6183}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *G-Quadruplexes ; Genome ; Humans ; Mitochondria ; Regulatory Sequences, Nucleic Acid/genetics ; }, abstract = {G-quadruplexes have important regulatory roles in the nuclear genome but their distribution and potential roles in mitochondrial DNA (mtDNA) are poorly understood. We analysed 11883 mtDNA sequences from 18 taxonomic sub-groups and identified their frequency and location within mtDNA. Large differences in both the frequency and number of putative quadruplex-forming sequences (PQS) were observed amongst all the organisms and PQS frequency was negatively correlated with an increase in evolutionary age. PQS were over-represented in the 3'UTRs, D-loops, replication origins, and stem loops, indicating regulatory roles for quadruplexes in mtDNA. Variations of the G-quadruplex-forming sequence in the conserved sequence block II (CSBII) region of the human D-loop were conserved amongst other mammals, amphibians, birds, reptiles, and fishes. This D-loop PQS was conserved in the duplicated control regions of some birds and reptiles, indicating its importance to mitochondrial function. The guanine tracts in these PQS also displayed significant length heterogeneity and the length of these guanine tracts were generally longest in bird mtDNA. This information provides further insights into how G4s may contribute to the regulation and function of mtDNA and acts as a database of information for future studies investigating mitochondrial G4s in organisms other than humans.}, } @article {pmid34941991, year = {2022}, author = {Song, MH and Yan, C and Li, JT}, title = {MEANGS: an efficient seed-free tool for de novo assembling animal mitochondrial genome using whole genome NGS data.}, journal = {Briefings in bioinformatics}, volume = {23}, number = {1}, pages = {}, doi = {10.1093/bib/bbab538}, pmid = {34941991}, issn = {1477-4054}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing/methods ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA ; Software ; Whole Genome Sequencing/*methods ; }, abstract = {Advances in next-generation sequencing (NGS) technologies have led to an exponential increase in the number of whole genome sequences (WGS) in databases. This wealth of WGS data has greatly facilitated the recovery of full mitochondrial genomes (mitogenomes), which are vital for phylogenetic, evolutionary and ecological studies. Unfortunately, most existing software cannot easily assemble mitogenome reference sequences conveniently or efficiently. Therefore, we developed a seed-free de novo assembly tool, MEANGS, which applies the trie-search method to extend contigs from self-discovery seeds and assemble a mitogenome from animal WGS data. We then used data from 16 species with different qualities to compare the performance of MEANGS with three other available programs. MEANGS exhibited the best overall performance since it was the only one that completed all tests, and it assembled full or partial mitogenomes for all of the tested samples while the others failed. Furthermore, MEANGS selects superior assembly sequences and annotates protein-coding genes. Thus, MEANGS can be one of the most efficient software for generating high-quality mitogenomes so far, the further use of it will benefit the study on mitogenome based on whole genome NGS data. MEANGS is available at https://github.com/YanCCscu/meangs.}, } @article {pmid34938509, year = {2021}, author = {Wade, MJ and Fogarty, L}, title = {Adaptive co-evolution of mitochondria and the Y-chromosome: A resolution to conflict between evolutionary opponents.}, journal = {Ecology and evolution}, volume = {11}, number = {23}, pages = {17307-17313}, pmid = {34938509}, issn = {2045-7758}, abstract = {In most species with motile sperm, male fertility depends upon genes located on the Y-chromosome and in the mitochondrial genome. Coordinated adaptive evolution for the function of male fertility between genes on the Y and the mitochondrion is hampered by their uniparental inheritance in opposing sexes: The Y-chromosome is inherited uniparentally, father to son, and the mitochondrion is inherited maternally, mother to offspring. Preserving male fertility is problematic, because maternal inheritance permits mitochondrial mutations advantageous to females, but deleterious to male fertility, to accumulate in a population. Although uniparental inheritance with sex-restricted adaptation also affects genes on the Y-chromosome, females lack a Y-chromosome and escape the potential maladaptive consequences of male-limited selection. Evolutionary models have shown that mitochondrial mutations deleterious to male fertility can be countered by compensatory evolution of Y-linked mutations that restore it. However, direct adaptive coevolution of Y- and mitochondrial gene combinations has not yet been mathematically characterized. We use population genetic models to show that adaptive coevolution of Y and mitochondrial genes are possible when Y-mt gene combinations have positive effects on male fertility and populations are inbred.}, } @article {pmid34934212, year = {2021}, author = {Donoso-Fuentes, A and Arriagada-Santis, D}, title = {[Organ dysfunction syndrome and mitochondrial adaptation in the septic patient].}, journal = {Boletin medico del Hospital Infantil de Mexico}, volume = {78}, number = {6}, pages = {597-611}, doi = {10.24875/BMHIM.20000323}, pmid = {34934212}, issn = {1665-1146}, mesh = {Humans ; Microcirculation ; Mitochondria ; *Multiple Organ Failure ; *Shock, Septic ; }, abstract = {The ability to maintain an adequate energy balance and to respond and adapt to environmental stress at the cellular level are cornerstones for the survival and evolution of organisms. Therefore, in the presence of various factors, a cellular protection response is triggered by activation of mitochondrial function-dependent signaling. However, this essential reaction for individual cell survival can be detrimental to organ function (maladaptation), transforming the close balance between the two into the pathogenetic axis of organ dysfunction and eventual recovery in septic patients. Macrocirculatory and microcirculatory disruption undoubtedly contributes to organ dysfunction in the early stage of septic shock, while intrinsic metabolic-bioenergetic failure (cytopathic hypoxia) perpetuates inadequate cellular function. Therefore, mitochondrial dysfunction is a key process in the induction of multiple organ dysfunction syndrome in the septic patient. This syndrome can be considered as a complex hypometabolic adaptive phenomenon in the face of excessive and prolonged inflammatory stimulus to achieve regulation of energy homeostasis and preservation of organ function. In the future, there should be a transition from the current consensus therapeutic options, which are limited to control of the infectious focus, hemodynamic and life support, to metabolic resuscitation based on the molecular and genetic alterations triggered by the infection.}, } @article {pmid34930424, year = {2021}, author = {Kelly, S}, title = {The economics of organellar gene loss and endosymbiotic gene transfer.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {345}, pmid = {34930424}, issn = {1474-760X}, mesh = {Arabidopsis/genetics ; Bacteria/*genetics ; Cell Nucleus ; Chloroplasts ; Gene Transfer, Horizontal ; *Genome, Chloroplast ; *Genome, Mitochondrial ; Genome, Plant ; Host Microbial Interactions/genetics ; Mitochondria/genetics ; Proteomics ; Symbiosis/*genetics ; }, abstract = {BACKGROUND: The endosymbiosis of the bacterial progenitors of the mitochondrion and the chloroplast are landmark events in the evolution of life on Earth. While both organelles have retained substantial proteomic and biochemical complexity, this complexity is not reflected in the content of their genomes. Instead, the organellar genomes encode fewer than 5% of the genes found in living relatives of their ancestors. While many of the 95% of missing organellar genes have been discarded, others have been transferred to the host nuclear genome through a process known as endosymbiotic gene transfer.

RESULTS: Here, we demonstrate that the difference in the per-cell copy number of the organellar and nuclear genomes presents an energetic incentive to the cell to either delete organellar genes or transfer them to the nuclear genome. We show that, for the majority of transferred organellar genes, the energy saved by nuclear transfer exceeds the costs incurred from importing the encoded protein into the organelle where it can provide its function. Finally, we show that the net energy saved by endosymbiotic gene transfer can constitute an appreciable proportion of total cellular energy budgets and is therefore sufficient to impart a selectable advantage to the cell.

CONCLUSION: Thus, reduced cellular cost and improved energy efficiency likely played a role in the reductive evolution of mitochondrial and chloroplast genomes and the transfer of organellar genes to the nuclear genome.}, } @article {pmid34925295, year = {2021}, author = {Fonseca, PLC and De-Paula, RB and Araújo, DS and Tomé, LMR and Mendes-Pereira, T and Rodrigues, WFC and Del-Bem, LE and Aguiar, ERGR and Góes-Neto, A}, title = {Global Characterization of Fungal Mitogenomes: New Insights on Genomic Diversity and Dynamism of Coding Genes and Accessory Elements.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {787283}, pmid = {34925295}, issn = {1664-302X}, abstract = {Fungi comprise a great diversity of species with distinct ecological functions and lifestyles. Similar to other eukaryotes, fungi rely on interactions with prokaryotes and one of the most important symbiotic events was the acquisition of mitochondria. Mitochondria are organelles found in eukaryotic cells whose main function is to generate energy through aerobic respiration. Mitogenomes (mtDNAs) are double-stranded circular or linear DNA from mitochondria that may contain core genes and accessory elements that can be replicated, transcribed, and independently translated from the nuclear genome. Despite their importance, investigative studies on the diversity of fungal mitogenomes are scarce. Herein, we have evaluated 788 curated fungal mitogenomes available at NCBI database to assess discrepancies and similarities among them and to better understand the mechanisms involved in fungal mtDNAs variability. From a total of 12 fungal phyla, four do not have any representative with available mitogenomes, which highlights the underrepresentation of some groups in the current available data. We selected representative and non-redundant mitogenomes based on the threshold of 90% similarity, eliminating 81 mtDNAs. Comparative analyses revealed considerable size variability of mtDNAs with a difference of up to 260 kb in length. Furthermore, variation in mitogenome length and genomic composition are generally related to the number and length of accessory elements (introns, HEGs, and uORFs). We identified an overall average of 8.0 (0-39) introns, 8.0 (0-100) HEGs, and 8.2 (0-102) uORFs per genome, with high variation among phyla. Even though the length of the core protein-coding genes is considerably conserved, approximately 36.3% of the mitogenomes evaluated have at least one of the 14 core coding genes absent. Also, our results revealed that there is not even a single gene shared among all mitogenomes. Other unusual genes in mitogenomes were also detected in many mitogenomes, such as dpo and rpo, and displayed diverse evolutionary histories. Altogether, the results presented in this study suggest that fungal mitogenomes are diverse, contain accessory elements and are absent of a conserved gene that can be used for the taxonomic classification of the Kingdom Fungi.}, } @article {pmid34919556, year = {2021}, author = {Lima-Cordón, RA and Cahan, SH and McCann, C and Dorn, PL and Justi, SA and Rodas, A and Monroy, MC and Stevens, L}, title = {Insights from a comprehensive study of Trypanosoma cruzi: A new mitochondrial clade restricted to North and Central America and genetic structure of TcI in the region.}, journal = {PLoS neglected tropical diseases}, volume = {15}, number = {12}, pages = {e0010043}, pmid = {34919556}, issn = {1935-2735}, mesh = {Central America ; Chagas Disease/*parasitology ; Electron Transport Complex I/genetics/metabolism ; Electron Transport Complex IV/genetics/metabolism ; Humans ; Mitochondria/*genetics/metabolism ; Phylogeny ; Protozoan Proteins/genetics/metabolism ; South America ; Trypanosoma cruzi/*classification/genetics/*isolation & purification ; }, abstract = {More than 100 years since the first description of Chagas Disease and with over 29,000 new cases annually due to vector transmission (in 2010), American Trypanosomiasis remains a Neglected Tropical Disease (NTD). This study presents the most comprehensive Trypanosoma cruzi sampling in terms of geographic locations and triatomine species analyzed to date and includes both nuclear and mitochondrial genomes. This addresses the gap of information from North and Central America. We incorporate new and previously published DNA sequence data from two mitochondrial genes, Cytochrome oxidase II (COII) and NADH dehydrogenase subunit 1 (ND1). These T. cruzi samples were collected over a broad geographic range including 111 parasite DNA samples extracted from triatomines newly collected across North and Central America, all of which were infected with T. cruzi in their natural environment. In addition, we present parasite reduced representation (Restriction site Associated DNA markers, RAD-tag) genomic nuclear data combined with the mitochondrial gene sequences for a subset of the triatomines (27 specimens) collected from Guatemala and El Salvador. Our mitochondrial phylogenetic reconstruction revealed two of the major mitochondrial lineages circulating across North and Central America, as well as the first ever mitochondrial data for TcBat from a triatomine collected in Central America. Our data also show that within mtTcIII, North and Central America represent an independent, distinct clade from South America, named here as mtTcIIINA-CA, geographically restricted to North and Central America. Lastly, the most frequent lineage detected across North and Central America, mtTcI, was also an independent, distinct clade from South America, noted as mtTcINA-CA. Furthermore, nuclear genome data based on Single Nucleotide Polymorphism (SNP) showed genetic structure of lineage TcI from specimens collected in Guatemala and El Salvador supporting the hypothesis that genetic diversity at a local scale has a geographical component. Our multiscale analysis contributes to the understanding of the independent and distinct evolution of T. cruzi lineages in North and Central America regions.}, } @article {pmid34917101, year = {2021}, author = {Nunes, JPS and Moraes-Vieira, PM and Chevillard, C and Cunha-Neto, E}, title = {Editorial: Mitochondria at the Crossroads of Immunity and Inflammatory Tissue Damage.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {810787}, doi = {10.3389/fimmu.2021.810787}, pmid = {34917101}, issn = {1664-3224}, support = {P50 AI098461/AI/NIAID NIH HHS/United States ; U19 AI098461/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; Immunity/*immunology ; Inflammation/*immunology ; Mitochondria/*immunology ; }, } @article {pmid34911545, year = {2021}, author = {Lewis, AJO and Hegde, RS}, title = {A unified evolutionary origin for the ubiquitous protein transporters SecY and YidC.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {266}, pmid = {34911545}, issn = {1741-7007}, support = {MC_ UP_A022_1007/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Bacterial Proteins/metabolism ; Cell Membrane/metabolism ; *Escherichia coli Proteins/metabolism ; Hydrophobic and Hydrophilic Interactions ; Membrane Proteins/genetics/metabolism ; Membrane Transport Proteins/genetics ; }, abstract = {BACKGROUND: Protein transporters translocate hydrophilic segments of polypeptide across hydrophobic cell membranes. Two protein transporters are ubiquitous and date back to the last universal common ancestor: SecY and YidC. SecY consists of two pseudosymmetric halves, which together form a membrane-spanning protein-conducting channel. YidC is an asymmetric molecule with a protein-conducting hydrophilic groove that partially spans the membrane. Although both transporters mediate insertion of membrane proteins with short translocated domains, only SecY transports secretory proteins and membrane proteins with long translocated domains. The evolutionary origins of these ancient and essential transporters are not known.

RESULTS: The features conserved by the two halves of SecY indicate that their common ancestor was an antiparallel homodimeric channel. Structural searches with SecY's halves detect exceptional similarity with YidC homologs. The SecY halves and YidC share a fold comprising a three-helix bundle interrupted by a helical hairpin. In YidC, this hairpin is cytoplasmic and facilitates substrate delivery, whereas in SecY, it is transmembrane and forms the substrate-binding lateral gate helices. In both transporters, the three-helix bundle forms a protein-conducting hydrophilic groove delimited by a conserved hydrophobic residue. Based on these similarities, we propose that SecY originated as a YidC homolog which formed a channel by juxtaposing two hydrophilic grooves in an antiparallel homodimer. We find that archaeal YidC and its eukaryotic descendants use this same dimerisation interface to heterodimerise with a conserved partner. YidC's sufficiency for the function of simple cells is suggested by the results of reductive evolution in mitochondria and plastids, which tend to retain SecY only if they require translocation of large hydrophilic domains.

CONCLUSIONS: SecY and YidC share previously unrecognised similarities in sequence, structure, mechanism, and function. Our delineation of a detailed correspondence between these two essential and ancient transporters enables a deeper mechanistic understanding of how each functions. Furthermore, key differences between them help explain how SecY performs its distinctive function in the recognition and translocation of secretory proteins. The unified theory presented here explains the evolution of these features, and thus reconstructs a key step in the origin of cells.}, } @article {pmid34905682, year = {2021}, author = {Niedźwiedzka-Rystwej, P and Bębnowska, D and Kołacz, R and Deptuła, W}, title = {Mitochondria, pattern recognition receptors and autophagy under physiological and pathological conditions, including viral infections.}, journal = {Acta biochimica Polonica}, volume = {69}, number = {1}, pages = {1-10}, doi = {10.18388/abp.2020_5807}, pmid = {34905682}, issn = {1734-154X}, mesh = {Animals ; Autophagy ; DNA, Mitochondrial/genetics ; Mammals/genetics/metabolism ; *Mitochondria/metabolism ; Receptors, Pattern Recognition/metabolism ; *Virus Diseases/metabolism ; }, abstract = {Research on the health of mammals invariably shows how dynamic immunology is and how the role of many elements and immune processes of the macroorganism, developed in the process of evolution in protecting against threats, including infections, is changing. Among these elements conditioning the homeostasis of the macroorganism are mitochondria, PRR receptors (pattern recognition receptors) and the phenomenon of autophagy. In the context of physiological and pathological states in the body, mitochondria perform various functions. The primary function of these organelles is to produce energy in the cell, but on the other hand, they are heavily involved in various cellular processes, including ROS production and calcium homeostasis. They are largely involved in the activation of immune mechanisms during infectious and non-infectious conditions through mtDNA and the mitochondrial MAVS protein. Mitochondrial involvement has been also determined in PRR-related mechanisms as mtDNA has the ability to directly stimulate TLRs. On the other hand, mitochondria are also associated with apoptotic cell death and autophagy.}, } @article {pmid34904040, year = {2021}, author = {Gopan, A and Sarma, MS}, title = {Mitochondrial hepatopathy: Respiratory chain disorders- 'breathing in and out of the liver'.}, journal = {World journal of hepatology}, volume = {13}, number = {11}, pages = {1707-1726}, pmid = {34904040}, issn = {1948-5182}, abstract = {Mitochondria, the powerhouse of a cell, are closely linked to the pathophysiology of various common as well as not so uncommon disorders of the liver and beyond. Evolution supports a prokaryotic descent, and, unsurprisingly, the organelle is worthy of being labeled an organism in itself. Since highly metabolically active organs require a continuous feed of energy, any dysfunction in the structure and function of mitochondria can have variable impact, with the worse end of the spectrum producing catastrophic consequences with a multisystem predisposition. Though categorized a hepatopathy, mitochondrial respiratory chain defects are not limited to the liver in time and space. The liver involvement is also variable in clinical presentation as well as in age of onset, from acute liver failure, cholestasis, or chronic liver disease. Other organs like eye, muscle, central and peripheral nervous system, gastrointestinal tract, hematological, endocrine, and renal systems are also variably involved. Diagnosis hinges on recognition of subtle clinical clues, screening metabolic investigations, evaluation of the extra-hepatic involvement, and role of genetics and tissue diagnosis. Treatment is aimed at both circumventing the acute metabolic crisis and long-term management including nutritional rehabilitation. This review lists and discusses the burden of mitochondrial respiratory chain defects, including various settings when to suspect, their evolution with time, including certain specific disorders, their tiered evaluation with diagnostic algorithms, management dilemmas, role of liver transplantation, and the future research tools.}, } @article {pmid34899176, year = {2021}, author = {Anoar, S and Woodling, NS and Niccoli, T}, title = {Mitochondria Dysfunction in Frontotemporal Dementia/Amyotrophic Lateral Sclerosis: Lessons From Drosophila Models.}, journal = {Frontiers in neuroscience}, volume = {15}, number = {}, pages = {786076}, pmid = {34899176}, issn = {1662-4548}, support = {MR/V003585/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by declining motor and cognitive functions. Even though these diseases present with distinct sets of symptoms, FTD and ALS are two extremes of the same disease spectrum, as they show considerable overlap in genetic, clinical and neuropathological features. Among these overlapping features, mitochondrial dysfunction is associated with both FTD and ALS. Recent studies have shown that cells derived from patients' induced pluripotent stem cells (iPSC)s display mitochondrial abnormalities, and similar abnormalities have been observed in a number of animal disease models. Drosophila models have been widely used to study FTD and ALS because of their rapid generation time and extensive set of genetic tools. A wide array of fly models have been developed to elucidate the molecular mechanisms of toxicity for mutations associated with FTD/ALS. Fly models have been often instrumental in understanding the role of disease associated mutations in mitochondria biology. In this review, we discuss how mutations associated with FTD/ALS disrupt mitochondrial function, and we review how the use of Drosophila models has been pivotal to our current knowledge in this field.}, } @article {pmid34890311, year = {2021}, author = {Zaccaron, AZ and Stergiopoulos, I}, title = {Characterization of the mitochondrial genomes of three powdery mildew pathogens reveals remarkable variation in size and nucleotide composition.}, journal = {Microbial genomics}, volume = {7}, number = {12}, pages = {}, pmid = {34890311}, issn = {2057-5858}, mesh = {Ascomycota/*genetics ; Base Composition ; Cytochromes b/genetics ; Erysiphe/*genetics ; Genome Size ; Genome, Fungal ; *Genome, Mitochondrial ; Introns ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Powdery mildews comprise a large group of economically important phytopathogenic fungi. However, limited information exists on their mitochondrial genomes. Here, we assembled and compared the mitochondrial genomes of the powdery mildew pathogens Blumeria graminis f. sp. tritici, Erysiphe pisi, and Golovinomyces cichoracearum. Included in the comparative analysis was also the mitochondrial genome of Erysiphe necator that was previously analysed. The mitochondrial genomes of the four Erysiphales exhibit a similar gene content and organization but a large variation in size, with sizes ranging from 109800 bp in B. graminis f. sp. tritici to 332165 bp in G. cichoracearum, which is the largest mitochondrial genome of a fungal pathogen reported to date. Further comparative analysis revealed an unusual bimodal GC distribution in the mitochondrial genomes of B. graminis f. sp. tritici and G. cichoracearum that was not previously observed in fungi. The cytochrome b (cob) genes of E. necator, E. pisi, and G. cichoracearum were also exceptionally rich in introns, which in turn harboured rare open reading frames encoding reverse transcriptases that were likely acquired horizontally. Golovinomyces cichoracearum had also the longest cob gene (45 kb) among 703 fungal cob genes analysed. Collectively, these results provide novel insights into the organization of mitochondrial genomes of powdery mildew pathogens and represent valuable resources for population genetics and evolutionary studies.}, } @article {pmid34887560, year = {2021}, author = {Guberovic, I and Hurtado-Bagès, S and Rivera-Casas, C and Knobloch, G and Malinverni, R and Valero, V and Leger, MM and García, J and Basquin, J and Gómez de Cedrón, M and Frigolé-Vivas, M and Cheema, MS and Pérez, A and Ausió, J and Ramírez de Molina, A and Salvatella, X and Ruiz-Trillo, I and Eirin-Lopez, JM and Ladurner, AG and Buschbeck, M}, title = {Evolution of a histone variant involved in compartmental regulation of NAD metabolism.}, journal = {Nature structural & molecular biology}, volume = {28}, number = {12}, pages = {1009-1019}, pmid = {34887560}, issn = {1545-9985}, mesh = {Cell Nucleus/metabolism ; Chromatin/metabolism ; DNA Repair/genetics ; Energy Metabolism/*physiology ; Eukaryota/metabolism ; Histones/*genetics/*metabolism ; Humans ; NAD/*metabolism ; Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors ; }, abstract = {NAD metabolism is essential for all forms of life. Compartmental regulation of NAD[+] consumption, especially between the nucleus and the mitochondria, is required for energy homeostasis. However, how compartmental regulation evolved remains unclear. In the present study, we investigated the evolution of the macrodomain-containing histone variant macroH2A1.1, an integral chromatin component that limits nuclear NAD[+] consumption by inhibiting poly(ADP-ribose) polymerase 1 in vertebrate cells. We found that macroH2A originated in premetazoan protists. The crystal structure of the macroH2A macrodomain from the protist Capsaspora owczarzaki allowed us to identify highly conserved principles of ligand binding and pinpoint key residue substitutions, selected for during the evolution of the vertebrate stem lineage. Metabolic characterization of the Capsaspora lifecycle suggested that the metabolic function of macroH2A was associated with nonproliferative stages. Taken together, we provide insight into the evolution of a chromatin element involved in compartmental NAD regulation, relevant for understanding its metabolism and potential therapeutic applications.}, } @article {pmid34887330, year = {2022}, author = {Zandi, M}, title = {ORF8/ORF8a: a difference between SARS-CoV-2 and SARS-CoV.}, journal = {The European respiratory journal}, volume = {59}, number = {2}, pages = {}, pmid = {34887330}, issn = {1399-3003}, mesh = {Biomarkers ; *COVID-19 ; Humans ; Phylogeny ; *SARS-CoV-2 ; }, abstract = {ORF8 as an accessory protein of SARS-CoV-2 https://bit.ly/3Gr3OTK}, } @article {pmid34880150, year = {2022}, author = {Hussain, M and Liaqat, I and Mubin, M and Nisar, B and Shahzad, K and Durrani, AI and Zafar, U and Afzaal, M and Ehsan, A and Rubab, S}, title = {DNA Barcoding: Molecular Identification and Phylogenetic Analysis of Pheretimoid Earthworm (Metaphire sp. and Amynthas sp.) Based on Mitochondrial Partial COI Gene from Sialkot, Pakistan.}, journal = {Journal of oleo science}, volume = {71}, number = {1}, pages = {83-93}, doi = {10.5650/jos.ess21246}, pmid = {34880150}, issn = {1347-3352}, mesh = {Animals ; DNA Barcoding, Taxonomic/*methods ; Electron Transport Complex IV/*genetics ; Mitochondria/*enzymology/*genetics ; Oligochaeta/anatomy & histology/classification/*genetics ; Pakistan ; *Phylogeny ; Species Specificity ; }, abstract = {The extremely difficult and challenging process is identifying pheretimoid species, genus Metaphire and Amynthas involving increased homoplasy in various morphological characteristics. The molecular identification, phylogenetic relationships, and evolutionary divergence time of earthworms belonging to the pheretimoid complex were investigated in this study using partial mitochondrial COI (cytochrome C oxidase subunit I) gene sequences ranging from 550-680 bp. Results revealed that 86 pheretimoid earthworms were morphologically different from a total of 342 mature worms. Moreover, 11 pheretimoid species were molecularly identified, including Metaphire posthuma (02), M. anomala (01), M. houlleti (02), M. californica (01), M. birmanica (02), Amynthas minimus (01), A. morrisi (01), and M. bununa (01). A phylogenetic tree was constructed with bootstrap values of 95%, which supported a monophyletic lineage of two well-supported clades formed by 12 partial COI sequences and 48 GenBank sequences using Hirudo medicinalis as an outgroup. The monophyly of these obtained genera indicated overall similarity at species level. Today, species like Amynthas, Metaphire and Pheretima have worm diversity in the form of pheretimoid earthworms, which dates to the Late Miocene (11.2-5.3 Mya) and the Pliocene (5.3-2.4 Mya). Compared to all relevant pheretimoid species, genetic p-distance values ranged from 0.0% to 0.57% (less than 1%). These low range values demonstrated that both genera Metaphire and Amynthas, supported the theory, which states that there are shared similarities among the species, despite different morphology. The current study is the first attempt in Pakistan to identify earthworms through DNA barcoding thus providing a genomic stamp. The work explored the significance of COI gene sequences to construct molecular tools that will be useful to overcome the different obstacles in morphologically similar earthworm identification and their phylogenetic study.}, } @article {pmid34858801, year = {2021}, author = {Dai, SD and Wang, S and Qin, YN and Zhu, JC}, title = {Multiomics Landscape Uncovers the Molecular Mechanism of the Malignant Evolution of Lung Adenocarcinoma Cells to Chronic Low Dose Cadmium Exposure.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {654687}, pmid = {34858801}, issn = {2234-943X}, abstract = {Cadmium (Cd) from cigarette smoke and polluted air can lead to lung adenocarcinoma after long-term inhalation. However, most studies are based on short-term exposure to this toxic metal at high concentrations. Here, we investigate the effects of long-term exposure of A549 cells (lung adenocarcinoma) to cadmium at low concentrations using morphological and multiomics analyses. First, we treated A549 cells continuously with CdCl2 at 1μM for 8 months and found that CdCl2 promoted cellular migration and invasion. After that, we applied transmission electron and fluorescence microscopies and did not observe significant morphological changes in Golgi apparatus, endoplasmic reticulum, lysosomes, or mitochondria on Cd treated cells; microfilaments, in contrast, accumulated in lamellipodium and adhesion plaques, which suggested that Cd enhanced cellular activity. Second, by using whole-exome sequencing (WES) we detected 4222 unique SNPs in Cd-treated cells, which included 382 unique non-synonymous mutation sites. The corresponding mutated genes, after GO and KEGG enrichments, were involved mainly in cell adhesion, movement, and metabolic pathways. Third, by RNA-seq analysis, we showed that 1250 genes (784 up and 466 down), 1623 mRNAs (1023 up and 591 down), and 679 lncRNAs (375 up and 304 down) were expressed differently. Furthermore, GO enrichment of these RNA-seq results suggested that most differentially expressed genes were related to cell adhesion and organization of the extracellular matrix in biological process terms; KEGG enrichment revealed that the differentially expressed genes took part in 26 pathways, among which the metabolic pathway was the most significant. These findings could be important for unveiling mechanisms of Cd-related cancers and for developing cancer therapies in the future.}, } @article {pmid34847540, year = {2021}, author = {Fernández Casafuz, AB and De Rossi, MC and Bruno, L}, title = {Morphological fluctuations of individual mitochondria in living cells.}, journal = {Journal of physics. Condensed matter : an Institute of Physics journal}, volume = {34}, number = {9}, pages = {}, doi = {10.1088/1361-648X/ac3e9c}, pmid = {34847540}, issn = {1361-648X}, mesh = {*Cytoskeleton/metabolism ; Microscopy, Confocal ; *Microtubules/metabolism ; Mitochondria/physiology ; Organelles ; }, abstract = {Uncovering the link between mitochondrial morphology, dynamics, positioning and function is challenging. Mitochondria are very flexible organelles that are subject to tension and compression within cells. Recent findings highlighted the importance of these mechanical aspects in the regulation of mitochondria dynamics, arising the question on which are the processes and mechanisms involved in their shape remodeling. In this work we explored in detail the morphological changes and spatio-temporal fluctuations of these organelles in livingXenopus laevismelanophores, a well-characterized cellular model. We developed an automatic method for the classification of mitochondria shapes based on the analysis of the curvature of the contour shape from confocal microscopy images. A persistence length of 2.1μm was measured, quantifying, for the first time, the bending plasticity of mitochondria in their cellular environment. The shape evolution at the single organelle level was followed during a few minutes revealing that mitochondria can bend and unbend in the seconds timescale. Furthermore, the inspection of confocal movies simultaneously registering fluorescent mitochondria and microtubules suggests that the cytoskeleton network architecture and dynamics play a significant role in mitochondria shape remodeling and fluctuations. For instance changes from sinuous to elongated organelles related to transitions from confined behavior to fast directed motion along microtubule tracks were observed.}, } @article {pmid34836918, year = {2021}, author = {Esteves, AR and Munoz-Pinto, MF and Nunes-Costa, D and Candeias, E and Silva, DF and Magalhães, JD and Pereira-Santos, AR and Ferreira, IL and Alarico, S and Tiago, I and Empadinhas, N and Cardoso, SM}, title = {Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria.}, journal = {Gut}, volume = {72}, number = {1}, pages = {73-89}, pmid = {34836918}, issn = {1468-3288}, abstract = {OBJECTIVE: Idiopathic Parkinson's disease (PD) is characterised by alpha-synuclein (aSyn) aggregation and death of dopaminergic neurons in the midbrain. Recent evidence posits that PD may initiate in the gut by microbes or their toxins that promote chronic gut inflammation that will ultimately impact the brain. In this work, we sought to demonstrate that the effects of the microbial toxin β-N-methylamino-L-alanine (BMAA) in the gut may trigger some PD cases, which is especially worrying as this toxin is present in certain foods but not routinely monitored by public health authorities.

DESIGN: To test the hypothesis, we treated wild-type mice, primary neuronal cultures, cell lines and isolated mitochondria with BMAA, and analysed its impact on gut microbiota composition, barrier permeability, inflammation and aSyn aggregation as well as in brain inflammation, dopaminergic neuronal loss and motor behaviour. To further examine the key role of mitochondria, we also determined the specific effects of BMAA on mitochondrial function and on inflammasome activation.

RESULTS: BMAA induced extensive depletion of segmented filamentous bacteria (SFB) that regulate gut immunity, thus triggering gut dysbiosis, immune cell migration, increased intestinal inflammation, loss of barrier integrity and caudo-rostral progression of aSyn. Additionally, BMAA induced in vitro and in vivo mitochondrial dysfunction with cardiolipin exposure and consequent activation of neuronal innate immunity. These events primed neuroinflammation, dopaminergic neuronal loss and motor deficits.

CONCLUSION: Taken together, our results demonstrate that chronic exposure to dietary BMAA can trigger a chain of events that recapitulate the evolution of the PD pathology from the gut to the brain, which is consistent with 'gut-first' PD.}, } @article {pmid34833151, year = {2021}, author = {Vargas-Mendoza, N and Angeles-Valencia, M and Morales-González, Á and Madrigal-Santillán, EO and Morales-Martínez, M and Madrigal-Bujaidar, E and Álvarez-González, I and Gutiérrez-Salinas, J and Esquivel-Chirino, C and Chamorro-Cevallos, G and Cristóbal-Luna, JM and Morales-González, JA}, title = {Oxidative Stress, Mitochondrial Function and Adaptation to Exercise: New Perspectives in Nutrition.}, journal = {Life (Basel, Switzerland)}, volume = {11}, number = {11}, pages = {}, pmid = {34833151}, issn = {2075-1729}, abstract = {Cells have the ability to adapt to stressful environments as a part of their evolution. Physical exercise induces an increase of a demand for energy that must be met by mitochondria as the main (ATP) provider. However, this process leads to the increase of free radicals and the so-called reactive oxygen species (ROS), which are necessary for the maintenance of cell signaling and homeostasis. In addition, mitochondrial biogenesis is influenced by exercise in continuous crosstalk between the mitochondria and the nuclear genome. Excessive workloads may induce severe mitochondrial stress, resulting in oxidative damage. In this regard, the objective of this work was to provide a general overview of the molecular mechanisms involved in mitochondrial adaptation during exercise and to understand if some nutrients such as antioxidants may be implicated in blunt adaptation and/or an impact on the performance of exercise by different means.}, } @article {pmid34831121, year = {2021}, author = {De Gaetano, A and Solodka, K and Zanini, G and Selleri, V and Mattioli, AV and Nasi, M and Pinti, M}, title = {Molecular Mechanisms of mtDNA-Mediated Inflammation.}, journal = {Cells}, volume = {10}, number = {11}, pages = {}, pmid = {34831121}, issn = {2073-4409}, mesh = {Biological Evolution ; Body Fluids/metabolism ; DNA, Mitochondrial/*genetics ; Extracellular Vesicles/metabolism ; Humans ; Inflammasomes/metabolism ; Inflammation/*genetics ; }, abstract = {Besides their role in cell metabolism, mitochondria display many other functions. Mitochondrial DNA (mtDNA), the own genome of the organelle, plays an important role in modulating the inflammatory immune response. When released from the mitochondrion to the cytosol, mtDNA is recognized by cGAS, a cGAMP which activates a pathway leading to enhanced expression of type I interferons, and by NLRP3 inflammasome, which promotes the activation of pro-inflammatory cytokines Interleukin-1beta and Interleukin-18. Furthermore, mtDNA can be bound by Toll-like receptor 9 in the endosome and activate a pathway that ultimately leads to the expression of pro-inflammatory cytokines. mtDNA is released in the extracellular space in different forms (free DNA, protein-bound DNA fragments) either as free circulating molecules or encapsulated in extracellular vesicles. In this review, we discussed the latest findings concerning the molecular mechanisms that regulate the release of mtDNA from mitochondria, and the mechanisms that connect mtDNA misplacement to the activation of inflammation in different pathophysiological conditions.}, } @article {pmid34829656, year = {2021}, author = {Hernández-Camacho, JD and García-Corzo, L and Fernández-Ayala, DJM and Navas, P and López-Lluch, G}, title = {Coenzyme Q at the Hinge of Health and Metabolic Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {34829656}, issn = {2076-3921}, abstract = {Coenzyme Q is a unique lipidic molecule highly conserved in evolution and essential to maintaining aerobic metabolism. It is endogenously synthesized in all cells by a very complex pathway involving a group of nuclear genes that share high homology among species. This pathway is tightly regulated at transcription and translation, but also by environment and energy requirements. Here, we review how coenzyme Q reacts within mitochondria to promote ATP synthesis and also integrates a plethora of metabolic pathways and regulates mitochondrial oxidative stress. Coenzyme Q is also located in all cellular membranes and plasma lipoproteins in which it exerts antioxidant function, and its reaction with different extramitochondrial oxidoreductases contributes to regulate the cellular redox homeostasis and cytosolic oxidative stress, providing a key factor in controlling various apoptosis mechanisms. Coenzyme Q levels can be decreased in humans by defects in the biosynthesis pathway or by mitochondrial or cytosolic dysfunctions, leading to a highly heterogeneous group of mitochondrial diseases included in the coenzyme Q deficiency syndrome. We also review the importance of coenzyme Q levels and its reactions involved in aging and age-associated metabolic disorders, and how the strategy of its supplementation has had benefits for combating these diseases and for physical performance in aging.}, } @article {pmid34829521, year = {2021}, author = {Olson, KR}, title = {A Case for Hydrogen Sulfide Metabolism as an Oxygen Sensing Mechanism.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {34829521}, issn = {2076-3921}, abstract = {The ability to detect oxygen availability is a ubiquitous attribute of aerobic organisms. However, the mechanism(s) that transduce oxygen concentration or availability into appropriate physiological responses is less clear and often controversial. This review will make the case for oxygen-dependent metabolism of hydrogen sulfide (H2S) and polysulfides, collectively referred to as reactive sulfur species (RSS) as a physiologically relevant O2 sensing mechanism. This hypothesis is based on observations that H2S and RSS metabolism is inversely correlated with O2 tension, exogenous H2S elicits physiological responses identical to those produced by hypoxia, factors that affect H2S production or catabolism also affect tissue responses to hypoxia, and that RSS efficiently regulate downstream effectors of the hypoxic response in a manner consistent with a decrease in O2. H2S-mediated O2 sensing is then compared to the more generally accepted reactive oxygen species (ROS) mediated O2 sensing mechanism and a number of reasons are offered to resolve some of the confusion between the two.}, } @article {pmid34828378, year = {2021}, author = {Chen, F and Zou, H and Jin, X and Zhang, D and Li, W and Li, M and Wu, S and Wang, G}, title = {Sequencing of the Complete Mitochondrial Genome of Pingus sinensis (Spirurina: Quimperiidae): Gene Arrangements and Phylogenetic Implications.}, journal = {Genes}, volume = {12}, number = {11}, pages = {}, pmid = {34828378}, issn = {2073-4425}, mesh = {Animals ; Bayes Theorem ; Codon Usage ; Evolution, Molecular ; Gene Order ; Genome Size ; Genome, Mitochondrial ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; Spirurina/*genetics/isolation & purification ; }, abstract = {Despite several decades of intensive research on spirurine nematodes, molecular data on some of the main lineages are still absent, which makes taxonomic classification insufficiently resolved. In the present study, we sequenced the first complete mitogenome for the family Quimperiidae, belonging to P. sinensis (Spirurina: Quimperiidae), a parasite living in the intestines of snakehead (Ophiocephalus argus). The circular mitogenome is 13,874 bp long, and it contains the standard nematode gene set: 22 transfer RNAs, 2 ribosomal RNAs and 12 protein-coding genes. There are also two long non-coding regions (NCR), in addition to only 8 other intergenic regions, ranging in size from 1 to 58 bp. To investigate its phylogenetic position and study the relationships among other available Spirurina, we performed the phylogenetic analysis using Bayesian inference and maximum likelihood approaches by concatenating the nucleotide sequences of all 36 genes on a dataset containing all available mitogenomes of the suborder Spirurina from NCBI and compared with gene order phylogenies using the MLGO program. Both supported the closer relationship of Ascaridoidea to Seuratoidea than to Spiruroidea. Pingus formed a sister-group with the Cucullanus genus. The results provide a new insights into the relationships within Spirurina.}, } @article {pmid34818432, year = {2022}, author = {Jiang, Y and Yue, L and Yang, F and Gillung, JP and Winterton, SL and Price, BW and Contreras-Ramos, A and Hayashi, F and Aspöck, U and Aspöck, H and Yeates, DK and Yang, D and Liu, X}, title = {Similar pattern, different paths: tracing the biogeographical history of Megaloptera (Insecta: Neuropterida) using mitochondrial phylogenomics.}, journal = {Cladistics : the international journal of the Willi Hennig Society}, volume = {38}, number = {3}, pages = {374-391}, doi = {10.1111/cla.12494}, pmid = {34818432}, issn = {1096-0031}, mesh = {Animals ; *Genome, Mitochondrial/genetics ; *Holometabola/genetics ; Insecta/genetics ; Mitochondria/genetics ; Phylogeny ; }, abstract = {The sequential breakup of the supercontinent Pangaea since the Middle Jurassic is one of the crucial factors that has driven the biogeographical patterns of terrestrial biotas. Despite decades of effort searching for concordant patterns between diversification and continental fragmentation among taxonomic groups, increasing evidence has revealed more complex and idiosyncratic scenarios resulting from a mixture of vicariance, dispersal and extinction. Aquatic insects with discreet ecological requirements, low vagility and disjunct distributions represent a valuable model for testing biogeographical hypotheses by reconstructing their distribution patterns and temporal divergences. Insects of the order Megaloptera have exclusively aquatic larvae, their adults have low vagility, and the group has a highly disjunct geographical distribution. Here we present a comprehensive phylogeny of Megaloptera based on a large-scale mitochondrial genome sequencing of 99 species representing >90% of the world genera from all major biogeographical regions. Molecular dating suggests that the deep divergence within Megaloptera pre-dates the breakup of Pangaea. Subsequently, the intergeneric divergences within Corydalinae (dobsonflies), Chauliodinae (fishflies) and Sialidae (alderflies) might have been driven by both vicariance and dispersal correlated with the shifting continent during the Cretaceous, but with strikingly different and incongruent biogeographical signals. The austral distribution of many corydalids appears to be a result of colonization from Eurasia through southward dispersal across Europe and Africa during the Cretaceous, whereas a nearly contemporaneous dispersal via northward rafting of Gondwanan landmasses may account for the colonization of extant Eurasian alderflies from the south.}, } @article {pmid34811145, year = {2021}, author = {Parrinha, D and Marques, MP and Heinicke, MP and Khalid, F and Parker, KL and Tolley, KA and Childers, JL and Conradie, W and Bauer, AM and Ceraco, LMP}, title = {A revision of Angolan species in the genus Pedioplanis Fitzinger (Squamata: Lacertidae), with the description of a new species.}, journal = {Zootaxa}, volume = {5032}, number = {1}, pages = {1-46}, doi = {10.11646/zootaxa.5032.1.1}, pmid = {34811145}, issn = {1175-5334}, mesh = {Animals ; Cell Nucleus ; *Lizards/genetics ; Mitochondria ; Phylogeny ; }, abstract = {The genus Pedioplanis reaches its northernmost limit in western Angola, where it is represented by three species, Pedioplanis benguelensis, P. haackei and P. huntleyi. The taxonomic status of P. benguelensis remains problematic, mainly due to the vague original description and the loss of the original type material. Here we provide a revision of the Angolan representatives of the genus, with the description of a new species, Pedioplanis serodioi sp. nov., from the lowlands of southwestern Angola. Phylogenetic analyses using a combination of mitochondrial (16S and ND2) and nuclear (RAG-1) markers, as well as morphological data, support the recognition of the new species. For purposes of nomenclatural stability, we designate a neotype for P. benguelensis and provide motivation to correct the spelling of the specific epithet to benguelensis. The clarification of the status of P. benguelensis and the description of a new species contribute to a better understanding of the taxonomy and biogeography of the genus Pedioplanis, as well as the general biogeographic context of southwestern Angola, adding to the growing evidence in favor of the recognition of this region as a hotspot of lizard diversity and endemism. An updated key to the genus is also provided.}, } @article {pmid34810731, year = {2021}, author = {Mousavi-Sabet, H and Eagderi, S and Vatandoust, S and Freyhof, J}, title = {Five new species of the sisorid catfish genus Glyptothorax from Iran (Teleostei: Sisoridae).}, journal = {Zootaxa}, volume = {5067}, number = {4}, pages = {451-484}, doi = {10.11646/zootaxa.5067.4.1}, pmid = {34810731}, issn = {1175-5334}, mesh = {Animals ; *Catfishes/genetics ; DNA, Mitochondrial ; Iran ; Mitochondria ; Rivers ; }, abstract = {Five new species of Glyptothorax are described from Iran. Glyptothorax alidaeii, new species, from the Seimare in the Karkheh drainage, G. galaxias, new species, from the upper Karun drainage, G. hosseinpanahii, new species, from the Zohreh drainage, G. pallens, new species, from the Sirvan drainage, and G. shapuri, new species, from Shapur in the Helleh drainage. Glyptothorax silviae from the Jarrahi drainage is re-diagnosed. All six species are morphologically distinguishable by the structure of the thoracic adhesive apparatus, as well as morphometric characters and details in the colour pattern. They form distinct mitochondrial clades between 1.2% and 4.1% minimum K2P distance based on the mitochondrial DNA barcode region.}, } @article {pmid34799698, year = {2021}, author = {Vowinckel, J and Hartl, J and Marx, H and Kerick, M and Runggatscher, K and Keller, MA and Mülleder, M and Day, J and Weber, M and Rinnerthaler, M and Yu, JSL and Aulakh, SK and Lehmann, A and Mattanovich, D and Timmermann, B and Zhang, N and Dunn, CD and MacRae, JI and Breitenbach, M and Ralser, M}, title = {The metabolic growth limitations of petite cells lacking the mitochondrial genome.}, journal = {Nature metabolism}, volume = {3}, number = {11}, pages = {1521-1535}, pmid = {34799698}, issn = {2522-5812}, support = {200829/WT_/Wellcome Trust/United Kingdom ; FC001134/MRC_/Medical Research Council/United Kingdom ; FC001134/ARC_/Arthritis Research UK/United Kingdom ; FC001134/CRUK_/Cancer Research UK/United Kingdom ; FC001134/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 260809/ERC_/European Research Council/International ; }, mesh = {Amino Acids/metabolism ; Biomass ; Cell Proliferation ; Citric Acid Cycle ; *Energy Metabolism ; Fungal Proteins/chemistry/genetics/metabolism ; *Genome, Mitochondrial ; Membrane Potential, Mitochondrial ; Mitochondria/*genetics/*metabolism ; Mutation ; Phenotype ; Structure-Activity Relationship ; Yeasts/*genetics/*metabolism ; }, abstract = {Eukaryotic cells can survive the loss of their mitochondrial genome, but consequently suffer from severe growth defects. 'Petite yeasts', characterized by mitochondrial genome loss, are instrumental for studying mitochondrial function and physiology. However, the molecular cause of their reduced growth rate remains an open question. Here we show that petite cells suffer from an insufficient capacity to synthesize glutamate, glutamine, leucine and arginine, negatively impacting their growth. Using a combination of molecular genetics and omics approaches, we demonstrate the evolution of fast growth overcomes these amino acid deficiencies, by alleviating a perturbation in mitochondrial iron metabolism and by restoring a defect in the mitochondrial tricarboxylic acid cycle, caused by aconitase inhibition. Our results hence explain the slow growth of mitochondrial genome-deficient cells with a partial auxotrophy in four amino acids that results from distorted iron metabolism and an inhibited tricarboxylic acid cycle.}, } @article {pmid34798191, year = {2021}, author = {Lin, Y and Xiao, Q and Hao, Q and Qian, Z and Li, X and Li, P and Li, H and Chen, L}, title = {Genome-wide identification and functional analysis of the glutathione S-transferase (GST) family in Pomacea canaliculata.}, journal = {International journal of biological macromolecules}, volume = {193}, number = {Pt B}, pages = {2062-2069}, doi = {10.1016/j.ijbiomac.2021.11.038}, pmid = {34798191}, issn = {1879-0003}, mesh = {Animals ; Cold-Shock Response/genetics ; Gastropoda/*genetics ; Genome/*genetics ; Glutathione Transferase/*genetics ; Oxidative Stress/genetics ; Phylogeny ; Reactive Oxygen Species/metabolism ; }, abstract = {Cold causes oxidative stress in living organisms, mainly caused by the accumulation of reactive oxygen species (ROS). In the antioxidant defense systems, Glutathione S-transferases (GSTs) play a vital role in the regulation of detoxification and redox balance of ROS. In this study, the P. canaliculata GST gene family were characterized using a genome-wide search of the conserved domain. Phylogenetic tree and domain composition analysis revealed that 30 PcGSTs belong to seven classes, including five in MAPEG, two in Mu, nine in Omega, 11 in Sigma, one in Rho, Theta and Alpha class, respectively. RNA-seq analysis revealed that most PcGSTs localized in mitochondria highly expressed in hepatopancreas, and most PcGSTs localized in cytoplasm highly expressed in kidney. A total of 12 PcGST genes were significantly up-regulated and PcGST12 was significantly down-regulated after cold acclimation. Ten PcGSTs were identified as DEGs under cold stress after cold acclimation. qRT-PCR revealed that the expression level of five PcGST genes were significantly varied during the cold acclimation. The present study investigated the characterization of the P. canaliculata GST gene family, extending our understanding of GST mediated cold acclimation and cold stress-response mechanisms in this invasive snail.}, } @article {pmid34797494, year = {2022}, author = {Yamazaki, D and Chiba, S}, title = {Comparing the genetic diversity and population structure of sister marine snails having contrasting habitat specificity.}, journal = {Molecular biology reports}, volume = {49}, number = {1}, pages = {393-401}, pmid = {34797494}, issn = {1573-4978}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; Gene Flow ; Genetic Variation ; Genetics, Population ; Japan ; Mitochondria/*genetics ; Phylogeny ; Phylogeography ; Snails/*classification/genetics ; Species Specificity ; }, abstract = {BACKGROUND: To grasp the processes of spatial genetic structuring in open and connectable marine environments is the principal study goal in molecular biological studies. Comparative seascape genetics using multiple species are a powerful approach to understand the physical geographic and oceanographic effects on genetic variation. Besides, species-specific ecological traits such as dispersal abilities and habitat specificity are important factors for spatial genetic structuring.

METHODS AND RESULTS: We focused on the sister marine snail species Tegula kusairo and T. xanthostigma around the Japanese mainland, which have contrasting habitat specificities for wave strength. Tegula kusairo only inhabits sheltered coastal environments, while T. xanthostigma is found mainly on wave-exposed rocky shores facing the open sea. We estimated their genetic diversity indices and levels of population differentiation based on mtDNA. We found that the genetic diversity of T. kusairo was lower than that of T. xanthostigma, while their level of population genetic differentiation was higher than that of T. xanthostigma. Namely, the species specific to weak wave environments had a higher level of population genetic differentiation than the species specific to strong wave action.

CONCLUSION: Ecological traits linked not only to dispersal abilities but also to habitat specificity can influence genetic variation in a pair of closely related sister species distributed in the same seascape.}, } @article {pmid34795357, year = {2021}, author = {Mishina, T and Takeshima, H and Takada, M and Iguchi, K and Zhang, C and Zhao, Y and Kawahara-Miki, R and Hashiguchi, Y and Tabata, R and Sasaki, T and Nishida, M and Watanabe, K}, title = {Interploidy gene flow involving the sexual-asexual cycle facilitates the diversification of gynogenetic triploid Carassius fish.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {22485}, pmid = {34795357}, issn = {2045-2322}, mesh = {Alleles ; Animals ; Asia ; Biological Evolution ; Cell Nucleus/metabolism ; DNA, Mitochondrial/genetics ; Diploidy ; Europe ; *Gene Flow ; Genetic Markers ; Genetics, Population ; Genotype ; Geography ; Goldfish/*genetics/*physiology ; Heterozygote ; Homozygote ; Japan/epidemiology ; Male ; Mitochondria/metabolism ; Models, Genetic ; Polymorphism, Single Nucleotide ; Principal Component Analysis ; Rivers ; Species Specificity ; Spermatozoa/physiology ; Transcriptome ; Triploidy ; }, abstract = {Asexual vertebrates are rare and at risk of extinction due to their restricted adaptability through the loss of genetic recombination. We explore the mechanisms behind the generation and maintenance of genetic diversity in triploid asexual (gynogenetic) Carassius auratus fish, which is widespread in East Asian fresh waters and exhibits one of the most extensive distribution among asexual vertebrates despite its dependence on host sperm. Our analyses of genetic composition using dozens of genetic markers and genome-wide transcriptome sequencing uncover admixed genetic composition of Japanese asexual triploid Carassius consisting of both the diverged Japanese and Eurasian alleles, suggesting the involvement of Eurasian lineages in its origin. However, coexisting sexual diploid relatives and asexual triploids in Japan show regional genetic similarity in both mitochondrial and nuclear markers. These results are attributed to a unique unidirectional gene flow from diploids to sympatric triploids, with the involvement of occasional sexual reproduction. Additionally, the asexual triploid shows a weaker population structure than the sexual diploid, and multiple triploid lineages coexist in most Japanese rivers. The generated diversity via repeated interploidy gene flow as well as an increased establishment of immigrants is assumed to offset the cost of asexual reproduction and might contribute to the successful broad distribution of this asexual vertebrate.}, } @article {pmid34789336, year = {2021}, author = {Proust, B and Radić, M and Vidaček, NŠ and Cottet, C and Attia, S and Lamarche, F and Ačkar, L and Mikulčić, VG and Tokarska-Schlattner, M and Ćetković, H and Schlattner, U and Bosnar, MH}, title = {NME6 is a phosphotransfer-inactive, monomeric NME/NDPK family member and functions in complexes at the interface of mitochondrial inner membrane and matrix.}, journal = {Cell & bioscience}, volume = {11}, number = {1}, pages = {195}, pmid = {34789336}, issn = {2045-3701}, abstract = {BACKGROUND: NME6 is a member of the nucleoside diphosphate kinase (NDPK/NME/Nm23) family which has key roles in nucleotide homeostasis, signal transduction, membrane remodeling and metastasis suppression. The well-studied NME1-NME4 proteins are hexameric and catalyze, via a phospho-histidine intermediate, the transfer of the terminal phosphate from (d)NTPs to (d)NDPs (NDP kinase) or proteins (protein histidine kinase). For the NME6, a gene/protein that emerged early in eukaryotic evolution, only scarce and partially inconsistent data are available. Here we aim to clarify and extend our knowledge on the human NME6.

RESULTS: We show that NME6 is mostly expressed as a 186 amino acid protein, but that a second albeit much less abundant isoform exists. The recombinant NME6 remains monomeric, and does not assemble into homo-oligomers or hetero-oligomers with NME1-NME4. Consequently, NME6 is unable to catalyze phosphotransfer: it does not generate the phospho-histidine intermediate, and no NDPK activity can be detected. In cells, we could resolve and extend existing contradictory reports by localizing NME6 within mitochondria, largely associated with the mitochondrial inner membrane and matrix space. Overexpressing NME6 reduces ADP-stimulated mitochondrial respiration and complex III abundance, thus linking NME6 to dysfunctional oxidative phosphorylation. However, it did not alter mitochondrial membrane potential, mass, or network characteristics. Our screen for NME6 protein partners revealed its association with NME4 and OPA1, but a direct interaction was observed only with RCC1L, a protein involved in mitochondrial ribosome assembly and mitochondrial translation, and identified as essential for oxidative phosphorylation.

CONCLUSIONS: NME6, RCC1L and mitoribosomes localize together at the inner membrane/matrix space where NME6, in concert with RCC1L, may be involved in regulation of the mitochondrial translation of essential oxidative phosphorylation subunits. Our findings suggest new functions for NME6, independent of the classical phosphotransfer activity associated with NME proteins.}, } @article {pmid34786732, year = {2022}, author = {Bykov, YS and Flohr, T and Boos, F and Zung, N and Herrmann, JM and Schuldiner, M}, title = {Widespread use of unconventional targeting signals in mitochondrial ribosome proteins.}, journal = {The EMBO journal}, volume = {41}, number = {1}, pages = {e109519}, pmid = {34786732}, issn = {1460-2075}, mesh = {Amino Acid Motifs ; Bacterial Proteins/chemistry ; Mitochondria/metabolism ; Mitochondrial Proteins/*metabolism ; Mitochondrial Ribosomes/*metabolism ; Models, Biological ; *Protein Sorting Signals ; Saccharomyces cerevisiae/*metabolism ; Sequence Homology, Amino Acid ; }, abstract = {Mitochondrial ribosomes are complex molecular machines indispensable for respiration. Their assembly involves the import of several dozens of mitochondrial ribosomal proteins (MRPs), encoded in the nuclear genome, into the mitochondrial matrix. Proteomic and structural data as well as computational predictions indicate that up to 25% of yeast MRPs do not have a conventional N-terminal mitochondrial targeting signal (MTS). We experimentally characterized a set of 15 yeast MRPs in vivo and found that five use internal MTSs. Further analysis of a conserved model MRP, Mrp17/bS6m, revealed the identity of the internal targeting signal. Similar to conventional MTS-containing proteins, the internal sequence mediates binding to TOM complexes. The entire sequence of Mrp17 contains positive charges mediating translocation. The fact that these sequence properties could not be reliably predicted by standard methods shows that mitochondrial protein targeting is more versatile than expected. We hypothesize that structural constraints imposed by ribosome assembly interfaces may have disfavored N-terminal presequences and driven the evolution of internal targeting signals in MRPs.}, } @article {pmid34784177, year = {2021}, author = {Holehouse, AS and Ginell, GM and Griffith, D and Böke, E}, title = {Clustering of Aromatic Residues in Prion-like Domains Can Tune the Formation, State, and Organization of Biomolecular Condensates.}, journal = {Biochemistry}, volume = {60}, number = {47}, pages = {3566-3581}, pmid = {34784177}, issn = {1520-4995}, mesh = {Amino Acids, Aromatic/chemistry/genetics/metabolism ; Animals ; Biomolecular Condensates/*metabolism ; Cell Polarity ; Cells, Cultured ; Female ; Intravital Microscopy ; Oocytes/cytology/metabolism ; Phase Transition ; Primary Cell Culture ; Protein Domains/genetics ; Protein Engineering ; T-Box Domain Proteins/chemistry/genetics/*metabolism ; Xenopus Proteins/chemistry/genetics/*metabolism ; Xenopus laevis ; }, abstract = {In immature oocytes, Balbiani bodies are conserved membraneless condensates implicated in oocyte polarization, the organization of mitochondria, and long-term organelle and RNA storage. In Xenopus laevis, Balbiani body assembly is mediated by the protein Velo1. Velo1 contains an N-terminal prion-like domain (PLD) that is essential for Balbiani body formation. PLDs have emerged as a class of intrinsically disordered regions that can undergo various different types of intracellular phase transitions and are often associated with dynamic, liquid-like condensates. Intriguingly, the Velo1 PLD forms solid-like assemblies. Here we sought to understand why Velo1 phase behavior appears to be biophysically distinct from that of other PLD-containing proteins. Through bioinformatic analysis and coarse-grained simulations, we predict that the clustering of aromatic residues and the amino acid composition of residues between aromatics can influence condensate material properties, organization, and the driving forces for assembly. To test our predictions, we redesigned the Velo1 PLD to test the impact of targeted sequence changes in vivo. We found that the Velo1 design with evenly spaced aromatic residues shows rapid internal dynamics, as probed by fluorescent recovery after photobleaching, even when recruited into Balbiani bodies. Our results suggest that Velo1 might have been selected in evolution for distinctly clustered aromatic residues to maintain the structure of Balbiani bodies in long-lived oocytes. In general, our work identifies several tunable parameters that can be used to augment the condensate material state, offering a road map for the design of synthetic condensates.}, } @article {pmid34783988, year = {2022}, author = {López-Cuamatzi, IL and Ortega, J and Baeza, JA}, title = {The complete mitochondrial genome of the 'Zacatuche' Volcano rabbit (Romerolagus diazi), an endemic and endangered species from the Volcanic Belt of Central Mexico.}, journal = {Molecular biology reports}, volume = {49}, number = {2}, pages = {1141-1149}, pmid = {34783988}, issn = {1573-4978}, mesh = {Animals ; Conservation of Natural Resources/methods ; Endangered Species ; Gene Order ; Genome, Mitochondrial/*genetics ; Lagomorpha/*genetics ; Mexico ; Mitochondria/*genetics ; Phylogeny ; RNA, Transfer/genetics ; Rabbits/genetics ; }, abstract = {BACKGROUND: The 'Zacatuche', 'Teporingo', or Volcano rabbit (Romerolagus diazi) belongs to the family Leporidae, is an endemic species restricted to the Central part of the Trans-Mexican Volcanic Belt, and is considered 'endangered' by the IUCN Red List of Threatened Species.

METHODS AND RESULTS: This study reports, for the first time, the complete mitochondrial genome of R. diazi and examined the phylogenetic position of R. diazi among other closely related co-familiar species using mitochondrial protein-coding genes (PCGs). The mitogenome of R. diazi was assembled from short Illumina 150 bp pair-end reads with a coverage of 189x. The AT-rich mitochondrial genome of R. diazi is 17,400 bp in length and is comprised of 13 PCGs, two ribosomal RNA genes, and 22 transfer RNA genes. The gene order observed in the mitochondrial genome of R. diazi is identical to that reported for other leporids. Phylogenetic analyses based on PCGs support the basal position of Romerolagus within the Leporidae, at least when compared to the genera Oryctolagus and Lepus. Nonetheless, additional mitochondrial genomes from species belonging to the genera Bunolagus, Sylvilagus, and Pronolagus, among others, are needed before a more robust conclusion about the derived vs basal placement of Romerolagus within the family Leporidae can be reached based on mitochondrial PCGs.

CONCLUSIONS: This is the first genomic resource developed for R. diazi and it represents a tool to improve our understanding about the ecology and evolutionary biology of this iconic and endangered species.}, } @article {pmid34781749, year = {2021}, author = {Benhamou, S and Rahioui, I and Henri, H and Charles, H and Da Silva, P and Heddi, A and Vavre, F and Desouhant, E and Calevro, F and Mouton, L}, title = {Cytotype Affects the Capability of the Whitefly Bemisia tabaci MED Species To Feed and Oviposit on an Unfavorable Host Plant.}, journal = {mBio}, volume = {12}, number = {6}, pages = {e0073021}, pmid = {34781749}, issn = {2150-7511}, mesh = {Amino Acids/chemistry ; Animals ; Feeding Behavior ; Fertility ; Hemiptera/classification/*physiology ; Hibiscus/chemistry/*parasitology/physiology ; Host Specificity ; Lantana/chemistry/*parasitology/physiology ; Mitochondria/metabolism ; Oviposition ; Symbiosis ; Tobacco/chemistry/*parasitology/physiology ; }, abstract = {The acquisition of nutritional obligate primary endosymbionts (P-symbionts) allowed phloemo-phageous insects to feed on plant sap and thus colonize novel ecological niches. P-symbionts often coexist with facultative secondary endosymbionts (S-symbionts), which may also influence their hosts' niche utilization ability. The whitefly Bemisia tabaci is a highly diversified species complex harboring, in addition to the P-symbiont "Candidatus Portiera aleyrodidarum," seven S-symbionts whose roles remain poorly understood. Here, we compare the phenotypic and metabolic responses of three B. tabaci lines differing in their S-symbiont community, reared on three different host plants, hibiscus, tobacco, or lantana, and address whether and how S-symbionts influence insect capacity to feed and produce offspring on those plants. We first show that hibiscus, tobacco, and lantana differ in their free amino acid composition. Insects' performance, as well as free amino acid profile and symbiotic load, were shown to be plant dependent, suggesting a critical role for the plant nutritional properties. Insect fecundity was significantly lower on lantana, indicating that it is the least favorable plant. Remarkably, insects reared on this plant show a specific amino acid profile and a higher symbiont density compared to the two other plants. In addition, this plant was the only one for which fecundity differences were observed between lines. Using genetically homogeneous hybrids, we demonstrate that cytotype (mitochondria and symbionts), and not genotype, is a major determinant of females' fecundity and amino acid profile on lantana. As cytotypes differ in their S-symbiont community, we propose that these symbionts may mediate their hosts' suitable plant range. IMPORTANCE Microbial symbionts are universal in eukaryotes, and it is now recognized that symbiotic associations represent major evolutionary driving forces. However, the extent to which symbionts contribute to their hosts' ecological adaptation and subsequent diversification is far from being fully elucidated. The whitefly Bemisia tabaci is a sap feeder associated with multiple coinfecting intracellular facultative symbionts. Here, we show that plant species simultaneously affect whiteflies' performance, amino acid profile, and symbiotic density, which could be partially explained by differences in plant nutritional properties. We also demonstrate that, on lantana, the least favorable plant used in our study, whiteflies' performance is determined by their cytotype. We propose that the host plant utilization in B. tabaci is influenced by its facultative symbiont community composition, possibly through its impact on the host dietary requirements. Altogether, our data provide new insights into the impact of intracellular microorganisms on their animal hosts' ecological niche range and diversification.}, } @article {pmid34773990, year = {2021}, author = {Liu, Y and Qu, J and Shi, Z and Zhang, P and Ren, M}, title = {Comparative genomic analysis of the tricarboxylic acid cycle members in four Solanaceae vegetable crops and expression pattern analysis in Solanum tuberosum.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {821}, pmid = {34773990}, issn = {1471-2164}, mesh = {Citric Acid Cycle/genetics ; Genomics ; Phylogeny ; *Solanum tuberosum/genetics ; Vegetables ; }, abstract = {BACKGROUND: The tricarboxylic acid (TCA) cycle is crucial for energy supply in animal, plant, and microbial cells. It is not only the main pathway of carbohydrate catabolism but also the final pathway of lipid and protein catabolism. Some TCA genes have been found to play important roles in the growth and development of tomato and potato, but no comprehensive study of TCA cycle genes in Solanaceae crops has been reported.

RESULTS: In this study, we analyzed TCA cycle genes in four important Solanaceae vegetable crops (potato (Solanum tuberosum), tomato (Solanum lycopersicum), eggplant (Solanum melongena), and pepper (Capsicum annuum)) based on comparative genomics. The four Solanaceae crops had a total of 180 TCA cycle genes: 43 in potato, 44 in tomato, 40 in eggplant, and 53 in pepper. Phylogenetic analysis, collinearity analysis, and tissue expression patterns revealed the conservation of and differences in TCA cycle genes between the four Solanaceae crops and found that there were unique subgroup members in Solanaceae crops that were independent of Arabidopsis genes. The expression analysis of potato TCA cycle genes showed that (1) they were widely expressed in various tissues, and some transcripts like Soltu.DM.01G003320.1(SCoAL) and Soltu.DM.04G021520.1 (SDH) mainly accumulate in vegetative organs, and some transcripts such as Soltu.DM.12G005620.3 (SDH) and Soltu.DM.02G007400.4 (MDH) are preferentially expressed in reproductive organs; (2) several transcripts can be significantly induced by hormones, such as Soltu.DM.08G023870.2 (IDH) and Soltu.DM.06G029290.1 (SDH) under ABA treatment, and Soltu.DM.07G021850.2 (CSY) and Soltu.DM.09G026740.1 (MDH) under BAP treatment, and Soltu.DM.02G000940.1 (IDH) and Soltu.DM.01G031350.4 (MDH) under GA treatment; (3) Soltu.DM.11G024650.1 (SDH) can be upregulated by the three disease resistance inducers including Phytophthora infestans, acibenzolar-S-methyl (BTH), and DL-β-amino-n-butyric acid (BABA); and (4) the levels of Soltu.DM.01G045790.1 (MDH), Soltu.DM.01G028520.3 (CSY), and Soltu.DM.12G028700.1 (CSY) can be activated by both NaCl and mannitol. The subcellular localization results of three potato citrate synthases showed that Soltu.DM.01G028520.3 was localized in mitochondria, while Soltu.DM.12G028700.1 and Soltu.DM.07G021850.1 were localized in the cytoplasm.

CONCLUSIONS: This study provides a scientific foundation for the comprehensive understanding and functional studies of TCA cycle genes in Solanaceae crops and reveals their potential roles in potato growth, development, and stress response.}, } @article {pmid34773616, year = {2022}, author = {Skuza, L}, title = {Primer Design for the Analysis of Closely Related Species: Application of Noncoding mtDNA and cpDNA Sequences.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2392}, number = {}, pages = {83-91}, pmid = {34773616}, issn = {1940-6029}, mesh = {Chloroplasts/genetics ; DNA, Chloroplast/genetics ; DNA, Mitochondrial/genetics ; *Mitochondria/genetics ; Phylogeny ; Plants/genetics ; Secale/genetics ; }, abstract = {Noncoding regions of the chloroplast (cpDNA) and mitochondrial (mtDNA) genomes are commonly used in plant phylogenetic and population studies. Consensus primers, which are homologous to most coding regions, but amplify variable noncoding regions, are very useful for this purpose. However, high genetic diversity of plants poses a problem in developing molecular methods that require conserved DNA sequences between species.This chapter describes the protocol for designing PCR primers suitable for analysis of closely related plant species. As an example, we used PCR primer design for cpDNA noncoding regions of the rye (Secale).}, } @article {pmid34752746, year = {2021}, author = {Erinjeri, AP and Labbadia, J}, title = {The importance of long-lived proteins: Not just nuclear anymore.}, journal = {Developmental cell}, volume = {56}, number = {21}, pages = {2925-2927}, doi = {10.1016/j.devcel.2021.10.015}, pmid = {34752746}, issn = {1878-1551}, mesh = {*Electron Transport Complex IV/metabolism ; *Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; }, abstract = {The significance of mitochondrial long-lived proteins (mitoLLPs) to tissue health has remained mysterious for over a decade. In this issue of Developmental Cell, Krishna et al. demonstrate that mitochondrial lifetimes are highly heterogeneous and that mitoLLPs promote respiratory capacity by facilitating supercomplex assembly within the electron transport chain.}, } @article {pmid34748935, year = {2022}, author = {Boël, M and Veyrunes, F and Durieux, AC and Freyssenet, D and Voituron, Y and Roussel, D}, title = {Does high mitochondrial efficiency carry an oxidative cost? The case of the African pygmy mouse (Mus mattheyi).}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {264}, number = {}, pages = {111111}, doi = {10.1016/j.cbpa.2021.111111}, pmid = {34748935}, issn = {1531-4332}, mesh = {Adenosine Diphosphate/metabolism ; Animals ; Hydrogen Peroxide/metabolism ; Mice ; Mice, Inbred C57BL ; Mitochondria, Muscle/*metabolism ; Muscle, Skeletal/metabolism ; Oxidative Phosphorylation ; Oxidative Stress ; Oxygen Consumption ; Reactive Oxygen Species/metabolism ; Species Specificity ; }, abstract = {Skeletal muscle mitochondria of the African pygmy mouse Mus mattheyi exhibit markedly reduced oxygen consumption and ATP synthesis rates but a higher mitochondrial efficiency than what would be expected from allometric trends. In the present study, we assessed whether such reduction of mitochondrial activity in M. mattheyi can limit the oxidative stress associated with an increased generation of mitochondrial reactive oxygen species. We conducted a comparative study of mitochondrial oxygen consumption, H2O2 release, and electron leak (%H2O2/O) in skeletal muscle mitochondria isolated from the extremely small African pygmy mouse (M. mattheyi, ~5 g) and Mus musculus, which is a larger Mus species (~25 g). Mitochondria were energized with pyruvate, malate, and succinate, after which fluxes were measured at different steady-state rates of oxidative phosphorylation. Overall, M. mattheyi exhibited lower oxidative activity and higher electron leak than M. musculus, while the H2O2 release did not differ significantly between these two Mus species. We further found that the high coupling efficiency of skeletal muscle mitochondria from M. mattheyi was associated with high electron leak. Nevertheless, data also show that, despite the higher electron leak, the lower mitochondrial respiratory capacity of M. mattheyi limits the cost of a net increase in H2O2 release, which is lower than that expected for a mammals of this size.}, } @article {pmid34748608, year = {2021}, author = {Powers, MJ and Martz, LD and Burton, RS and Hill, GE and Weaver, RJ}, title = {Evidence for hybrid breakdown in production of red carotenoids in the marine invertebrate Tigriopus californicus.}, journal = {PloS one}, volume = {16}, number = {11}, pages = {e0259371}, pmid = {34748608}, issn = {1932-6203}, mesh = {Animals ; Aquatic Organisms ; Carotenoids/*metabolism ; Cell Nucleus/genetics/metabolism ; Copepoda/*genetics/metabolism ; *Genetic Fitness ; Hybridization, Genetic ; Invertebrates ; Mitochondria/genetics/metabolism ; Oxidative Phosphorylation ; Xanthophylls/metabolism ; }, abstract = {The marine copepod, Tigriopus californicus, produces the red carotenoid pigment astaxanthin from yellow dietary precursors. This 'bioconversion' of yellow carotenoids to red is hypothesized to be linked to individual condition, possibly through shared metabolic pathways with mitochondrial oxidative phosphorylation. Experimental inter-population crosses of lab-reared T. californicus typically produces low-fitness hybrids is due in large part to the disruption of coadapted sets nuclear and mitochondrial genes within the parental populations. These hybrid incompatibilities can increase variability in life history traits and energy production among hybrid lines. Here, we tested if production of astaxanthin was compromised in hybrid copepods and if it was linked to mitochondrial metabolism and offspring development. We observed no clear mitonuclear dysfunction in hybrids fed a limited, carotenoid-deficient diet of nutritional yeast. However, when yellow carotenoids were restored to their diet, hybrid lines produced less astaxanthin than parental lines. We observed that lines fed a yeast diet produced less ATP and had slower offspring development compared to lines fed a more complete diet of algae, suggesting the yeast-only diet may have obscured effects of mitonuclear dysfunction. Astaxanthin production was not significantly associated with development among lines fed a yeast diet but was negatively related to development in early generation hybrids fed an algal diet. In lines fed yeast, astaxanthin was negatively related to ATP synthesis, but in lines fed algae, the relationship was reversed. Although the effects of the yeast diet may have obscured evidence of hybrid dysfunction, these results suggest that astaxanthin bioconversion may still be related to mitochondrial performance and reproductive success.}, } @article {pmid34746119, year = {2021}, author = {Thomas, LW and Ashcroft, M}, title = {The Contextual Essentiality of Mitochondrial Genes in Cancer.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {695351}, pmid = {34746119}, issn = {2296-634X}, abstract = {Mitochondria are key organelles in eukaryotic evolution that perform crucial roles as metabolic and cellular signaling hubs. Mitochondrial function and dysfunction are associated with a range of diseases, including cancer. Mitochondria support cancer cell proliferation through biosynthetic reactions and their role in signaling, and can also promote tumorigenesis via processes such as the production of reactive oxygen species (ROS). The advent of (nuclear) genome-wide CRISPR-Cas9 deletion screens has provided gene-level resolution of the requirement of nuclear-encoded mitochondrial genes (NEMGs) for cancer cell viability (essentiality). More recently, it has become apparent that the essentiality of NEMGs is highly dependent on the cancer cell context. In particular, key tumor microenvironmental factors such as hypoxia, and changes in nutrient (e.g., glucose) availability, significantly influence the essentiality of NEMGs. In this mini-review we will discuss recent advances in our understanding of the contribution of NEMGs to cancer from CRISPR-Cas9 deletion screens, and discuss emerging concepts surrounding the context-dependent nature of mitochondrial gene essentiality.}, } @article {pmid34734993, year = {2022}, author = {Hüdig, M and Tronconi, MA and Zubimendi, JP and Sage, TL and Poschmann, G and Bickel, D and Gohlke, H and Maurino, VG}, title = {Respiratory and C4-photosynthetic NAD-malic enzyme coexist in bundle sheath cell mitochondria and evolved via association of differentially adapted subunits.}, journal = {The Plant cell}, volume = {34}, number = {1}, pages = {597-615}, pmid = {34734993}, issn = {1532-298X}, mesh = {Adaptation, Biological ; Capparaceae/*enzymology ; Cleome/enzymology ; *Evolution, Molecular ; Malate Dehydrogenase/*chemistry/metabolism ; Mitochondria/metabolism ; Plant Proteins/*chemistry/metabolism ; }, abstract = {In plant mitochondria, nicotinamide adenine dinucleotide-malic enzyme (NAD-ME) has a housekeeping function in malate respiration. In different plant lineages, NAD-ME was independently co-opted in C4 photosynthesis. In the C4 Cleome species, Gynandropsis gynandra and Cleome angustifolia, all NAD-ME genes (NAD-MEα, NAD-MEβ1, and NAD-MEβ2) were affected by C4 evolution and are expressed at higher levels than their orthologs in the C3 species Tarenaya hassleriana. In T. hassleriana, the NAD-ME housekeeping function is performed by two heteromers, NAD-MEα/β1 and NAD-MEα/β2, with similar biochemical properties. In both C4 species, this role is restricted to NAD-MEα/β2. In the C4 species, NAD-MEα/β1 is exclusively present in the leaves, where it accounts for most of the enzymatic activity. Gynandropsis gynandra NAD-MEα/β1 (GgNAD-MEα/β1) exhibits high catalytic efficiency and is differentially activated by the C4 intermediate aspartate, confirming its role as the C4-decarboxylase. During C4 evolution, NAD-MEβ1 lost its catalytic activity; its contribution to the enzymatic activity results from a stabilizing effect on the associated α-subunit and the acquisition of regulatory properties. We conclude that in bundle sheath cell mitochondria of C4 species, the functions of NAD-ME as C4 photosynthetic decarboxylase and as a housekeeping enzyme coexist and are performed by isoforms that combine the same α-subunit with differentially adapted β-subunits.}, } @article {pmid34728739, year = {2021}, author = {Wang, X and Li, LL and Xiao, Y and Chen, XY and Chen, JH and Hu, XS}, title = {A complete sequence of mitochondrial genome of Neolamarckia cadamba and its use for systematic analysis.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {21452}, pmid = {34728739}, issn = {2045-2322}, mesh = {DNA, Mitochondrial/analysis/*genetics ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics/metabolism ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Rubiaceae/*genetics/growth & development ; *Transcriptome ; }, abstract = {Neolamarckia cadamba is an important tropical and subtropical tree for timber industry in southern China and is also a medicinal plant because of the secondary product cadambine. N. cadamba belongs to Rubiaceae family and its taxonomic relationships with other species are not fully evaluated based on genome sequences. Here, we report the complete sequences of mitochondrial genome of N. cadamba, which is 414,980 bp in length and successfully assembled in two genome circles (109,836 bp and 305,144 bp). The mtDNA harbors 83 genes in total, including 40 protein-coding genes (PCGs), 31 transfer RNA genes, 6 ribosomal RNA genes, and 6 other genes. The base composition of the whole genome is estimated as 27.26% for base A, 22.63% for C, 22.53% for G, and 27.56% for T, with the A + T content of 54.82% (54.45% in the small circle and 54.79% in the large circle). Repetitive sequences account for ~ 0.14% of the whole genome. A maximum likelihood (ML) tree based on DNA sequences of 24 PCGs supports that N. cadamba belongs to order Gentianales. A ML tree based on rps3 gene of 60 species in family Rubiaceae shows that N. cadamba is more related to Cephalanthus accidentalis and Hymenodictyon parvifolium and belongs to the Cinchonoideae subfamily. The result indicates that N. cadamba is genetically distant from the species and genera of Rubiaceae in systematic position. As the first sequence of mitochondrial genome of N. cadamba, it will provide a useful resource to investigate genetic variation and develop molecular markers for genetic breeding in the future.}, } @article {pmid34727288, year = {2022}, author = {Liu, K and Xie, N and Ma, HJ}, title = {Next-generation sequencing reveals the mitogenomic heteroplasmy in the topmouth culter (Culter alburnus Basilewsky, 1855).}, journal = {Molecular biology reports}, volume = {49}, number = {2}, pages = {943-950}, pmid = {34727288}, issn = {1573-4978}, mesh = {Animals ; China ; Cyprinidae/*genetics ; Cypriniformes/genetics ; DNA, Mitochondrial/*genetics ; Fish Proteins/genetics ; Heteroplasmy/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Mitogens/genetics ; Phylogeny ; }, abstract = {BACKGROUND: The mitogenomic heteroplasmy is the presence of multiple haplotypes in the mitochondria, which could cause genetic diseases and is also associated with many critical biological functions. The topmouth culter (Culter alburnus Basilewsky, 1855) is one of the most important freshwater fish in the family of Cyprinidae in China. At present, there are no reports on the topmouth culter's mtDNA heteroplasmy and the existence of which is not known.

METHODS AND RESULTS: This study aimed to analyze the mitogenomic heteroplasmy in the topmouth culter by the next-generation sequencing of the fins' total DNA. The results confirmed the existence of the heteroplasmy and indicated the presence of the extensive heteroplasmy in the topmouth culter's mitogenome. There were 38 heteroplasmic variations in the protein-coding genes from the three specimens, with 33 non-synonymous substitutions accounting for 86.84% and five synonymous substitutions accounting for 13.16%. Among them, the ND6 had the most heteroplasmic variations but only one synonymous substitution. After removing the putative nuclear mitochondrial DNA fragments, the ratio of primary haplotype in the three specimens was 43.89%, 74.72%, and 32.76%, respectively. The three specimens contained 21, 7, and 21 haplotypes of the mitogenomes, respectively. Due to the extensive heteroplasmy, we reconstructed the phylogenetic tree of the topmouth culter using the RY-coding method, which improved the performance of the phylogenetic tree to some extent.

CONCLUSIONS: This study reported the mitogenomic heteroplasmy in the topmouth culter and enhanced the knowledge regarding the mitogenomic heteroplasmy in phylogenetic studies. As the topmouth culter is a commercial species, the mitogenomic heteroplasmy is crucial for the fisheries management of the topmouth culter.}, } @article {pmid34724985, year = {2021}, author = {Wu, Y and Wang, XH and Li, XH and Song, LY and Yu, SL and Fang, ZC and Liu, YQ and Yuan, LY and Peng, CY and Zhang, SY and Cheng, W and Ma, HC and Wang, LF and Tang, JM and Wang, YF and Ji, FY}, title = {Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China.}, journal = {Military Medical Research}, volume = {8}, number = {1}, pages = {57}, pmid = {34724985}, issn = {2054-9369}, mesh = {*COVID-19/genetics ; Case-Control Studies ; China ; *DNA, Mitochondrial/genetics ; Humans ; Mitochondria/genetics ; Phylogeny ; Risk Factors ; }, abstract = {BACKGROUND: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk.

METHODS: A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student's t-test was used for continuous variables, and Pearson's chi-squared test or Fisher's exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations.

RESULTS: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428-0.814, P = 0.001; and OR = 0.654, 95% CI 0.457-0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179-4.608, P = 0.015; OR = 2.033, 95% CI 1.242-3.322, P = 0.005; OR = 3.040, 95% CI 1.522-6.061, P = 0.002; and OR = 2.890, 95% CI 1.199-6.993, P = 0.018, respectively).

CONCLUSIONS: This is the first study to explore the association of mtDNA variants with individual's risk of developing severe COVID-19. Based on the case-control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual's resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual's risk of developing severe COVID-19.}, } @article {pmid34715011, year = {2021}, author = {Hochberg, I and Demain, LAM and Richer, J and Thompson, K and Urquhart, JE and Rea, A and Pagarkar, W and Rodríguez-Palmero, A and Schlüter, A and Verdura, E and Pujol, A and Quijada-Fraile, P and Amberger, A and Deutschmann, AJ and Demetz, S and Gillespie, M and Belyantseva, IA and McMillan, HJ and Barzik, M and Beaman, GM and Motha, R and Ng, KY and O'Sullivan, J and Williams, SG and Bhaskar, SS and Lawrence, IR and Jenkinson, EM and Zambonin, JL and Blumenfeld, Z and Yalonetsky, S and Oerum, S and Rossmanith, W and , and Yue, WW and Zschocke, J and Munro, KJ and Battersby, BJ and Friedman, TB and Taylor, RW and O'Keefe, RT and Newman, WG}, title = {Bi-allelic variants in the mitochondrial RNase P subunit PRORP cause mitochondrial tRNA processing defects and pleiotropic multisystem presentations.}, journal = {American journal of human genetics}, volume = {108}, number = {11}, pages = {2195-2204}, pmid = {34715011}, issn = {1537-6605}, mesh = {Adult ; *Alleles ; Female ; *Genetic Pleiotropy ; Humans ; Male ; Mitochondria/*enzymology ; Pedigree ; RNA, Mitochondrial/*genetics ; RNA, Transfer/*genetics ; Ribonuclease P/*genetics ; }, abstract = {Human mitochondrial RNase P (mt-RNase P) is responsible for 5' end processing of mitochondrial precursor tRNAs, a vital step in mitochondrial RNA maturation, and is comprised of three protein subunits: TRMT10C, SDR5C1 (HSD10), and PRORP. Pathogenic variants in TRMT10C and SDR5C1 are associated with distinct recessive or x-linked infantile onset disorders, resulting from defects in mitochondrial RNA processing. We report four unrelated families with multisystem disease associated with bi-allelic variants in PRORP, the metallonuclease subunit of mt-RNase P. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes. Fibroblasts from affected individuals in two families demonstrated decreased steady state levels of PRORP, an accumulation of unprocessed mitochondrial transcripts, and decreased steady state levels of mitochondrial-encoded proteins, which were rescued by introduction of the wild-type PRORP cDNA. In mt-tRNA processing assays performed with recombinant mt-RNase P proteins, the disease-associated variants resulted in diminished mitochondrial tRNA processing. Identification of disease-causing variants in PRORP indicates that pathogenic variants in all three subunits of mt-RNase P can cause mitochondrial dysfunction, each with distinct pleiotropic clinical presentations.}, } @article {pmid34713507, year = {2022}, author = {Balparda, M and Elsässer, M and Badia, MB and Giese, J and Bovdilova, A and Hüdig, M and Reinmuth, L and Eirich, J and Schwarzländer, M and Finkemeier, I and Schallenberg-Rüdinger, M and Maurino, VG}, title = {Acetylation of conserved lysines fine-tunes mitochondrial malate dehydrogenase activity in land plants.}, journal = {The Plant journal : for cell and molecular biology}, volume = {109}, number = {1}, pages = {92-111}, doi = {10.1111/tpj.15556}, pmid = {34713507}, issn = {1365-313X}, mesh = {Acetylation ; Embryophyta/*enzymology/genetics ; Lysine/metabolism ; Malate Dehydrogenase/genetics/*metabolism ; Mitochondria/enzymology ; Mitochondrial Proteins/genetics/metabolism ; Plant Proteins/genetics/metabolism ; *Protein Processing, Post-Translational ; }, abstract = {Plants need to rapidly and flexibly adjust their metabolism to changes of their immediate environment. Since this necessity results from the sessile lifestyle of land plants, key mechanisms for orchestrating central metabolic acclimation are likely to have evolved early. Here, we explore the role of lysine acetylation as a post-translational modification to directly modulate metabolic function. We generated a lysine acetylome of the moss Physcomitrium patens and identified 638 lysine acetylation sites, mostly found in mitochondrial and plastidial proteins. A comparison with available angiosperm data pinpointed lysine acetylation as a conserved regulatory strategy in land plants. Focusing on mitochondrial central metabolism, we functionally analyzed acetylation of mitochondrial malate dehydrogenase (mMDH), which acts as a hub of plant metabolic flexibility. In P. patens mMDH1, we detected a single acetylated lysine located next to one of the four acetylation sites detected in Arabidopsis thaliana mMDH1. We assessed the kinetic behavior of recombinant A. thaliana and P. patens mMDH1 with site-specifically incorporated acetyl-lysines. Acetylation of A. thaliana mMDH1 at K169, K170, and K334 decreases its oxaloacetate reduction activity, while acetylation of P. patens mMDH1 at K172 increases this activity. We found modulation of the malate oxidation activity only in A. thaliana mMDH1, where acetylation of K334 strongly activated it. Comparative homology modeling of MDH proteins revealed that evolutionarily conserved lysines serve as hotspots of acetylation. Our combined analyses indicate lysine acetylation as a common strategy to fine-tune the activity of central metabolic enzymes with likely impact on plant acclimation capacity.}, } @article {pmid34710348, year = {2021}, author = {Stairs, CW and Táborský, P and Salomaki, ED and Kolisko, M and Pánek, T and Eme, L and Hradilová, M and Vlček, Č and Jerlström-Hultqvist, J and Roger, AJ and Čepička, I}, title = {Anaeramoebae are a divergent lineage of eukaryotes that shed light on the transition from anaerobic mitochondria to hydrogenosomes.}, journal = {Current biology : CB}, volume = {31}, number = {24}, pages = {5605-5612.e5}, doi = {10.1016/j.cub.2021.10.010}, pmid = {34710348}, issn = {1879-0445}, mesh = {Anaerobiosis ; *Eukaryota/metabolism ; Mitochondria/genetics/metabolism ; *Organelles/genetics/metabolism ; Oxygen/metabolism ; Phylogeny ; }, abstract = {Discoveries of diverse microbial eukaryotes and their inclusion in comprehensive phylogenomic analyses have crucially re-shaped the eukaryotic tree of life in the 21st century.[1] At the deepest level, eukaryotic diversity comprises 9-10 "supergroups." One of these supergroups, the Metamonada, is particularly important to our understanding of the evolutionary dynamics of eukaryotic cells, including the remodeling of mitochondrial function. All metamonads thrive in low-oxygen environments and lack classical aerobic mitochondria, instead possessing mitochondrion-related organelles (MROs) with metabolisms that are adapted to low-oxygen conditions. These MROs lack an organellar genome, do not participate in the Krebs cycle and oxidative phosphorylation,[2] and often synthesize ATP by substrate-level phosphorylation coupled to hydrogen production.[3][,][4] The events that occurred during the transition from an oxygen-respiring mitochondrion to a functionally streamlined MRO early in metamonad evolution remain largely unknown. Here, we report transcriptomes of two recently described, enigmatic, anaerobic protists from the genus Anaeramoeba.[5] Using phylogenomic analysis, we show that these species represent a divergent, phylum-level lineage in the tree of metamonads, emerging as a sister group of the Parabasalia and reordering the deep branching order of the metamonad tree. Metabolic reconstructions of the Anaeramoeba MROs reveal many "classical" mitochondrial features previously not seen in metamonads, including a disulfide relay import system, propionate production, and amino acid metabolism. Our findings suggest that the cenancestor of Metamonada likely had MROs with more classical mitochondrial features than previously anticipated and demonstrate how discoveries of novel lineages of high taxonomic rank continue to transform our understanding of early eukaryote evolution.}, } @article {pmid34704591, year = {2021}, author = {Kato, S and Arasaki, K and Tokutomi, N and Imai, Y and Inoshita, T and Hattori, N and Sasaki, T and Sato, M and Wakana, Y and Inoue, H and Tagaya, M}, title = {Syntaxin 17, an ancient SNARE paralog, plays different and conserved roles in different organisms.}, journal = {Journal of cell science}, volume = {134}, number = {22}, pages = {}, doi = {10.1242/jcs.258699}, pmid = {34704591}, issn = {1477-9137}, mesh = {Animals ; Autophagy ; HeLa Cells ; Humans ; *Membrane Fusion ; Qa-SNARE Proteins/genetics ; *SNARE Proteins ; }, abstract = {Mammalian syntaxin 17 (Stx17) has several roles in processes other than membrane fusion, including in mitochondrial division, autophagosome formation and lipid droplet expansion. In contrast to conventional syntaxins, Stx17 has a long C-terminal hydrophobic region with a hairpin-like structure flanked by a basic amino acid-enriched C-terminal tail. Although Stx17 is one of the six ancient SNAREs and is present in diverse eukaryotic organisms, it has been lost in multiple lineages during evolution. In the present study, we compared the localization and function of fly and nematode Stx17s expressed in HeLa cells with those of human Stx17. We found that fly Stx17 predominantly localizes to the cytosol and mediates autophagy, but not mitochondrial division. Nematode Stx17, on the other hand, is predominantly present in mitochondria and facilitates mitochondrial division, but is irrelevant to autophagy. These differences are likely due to different structures in the C-terminal tail. Non-participation of fly Stx17 and nematode Stx17 in mitochondrial division and autophagy, respectively, was demonstrated in individual organisms. Our results provide an insight into the evolution of Stx17 in metazoa. This article has an associated First Person interview with the first author of the paper.}, } @article {pmid34689722, year = {2022}, author = {Ahuja, P and Ng, CF and Pang, BPS and Chan, WS and Tse, MCL and Bi, X and Kwan, HR and Brobst, D and Herlea-Pana, O and Yang, X and Du, G and Saengnipanthkul, S and Noh, HL and Jiao, B and Kim, JK and Lee, CW and Ye, K and Chan, CB}, title = {Muscle-generated BDNF (brain derived neurotrophic factor) maintains mitochondrial quality control in female mice.}, journal = {Autophagy}, volume = {18}, number = {6}, pages = {1367-1384}, pmid = {34689722}, issn = {1554-8635}, support = {U2C DK093000/DK/NIDDK NIH HHS/United States ; }, mesh = {*AMP-Activated Protein Kinases/metabolism ; Animals ; Autophagy ; *Brain-Derived Neurotrophic Factor/metabolism ; Fatty Acids/metabolism ; Female ; Mice ; *Mitochondria, Muscle/metabolism ; *Muscle, Skeletal/physiology ; }, abstract = {Mitochondrial remodeling is dysregulated in metabolic diseases but the underlying mechanism is not fully understood. We report here that BDNF (brain derived neurotrophic factor) provokes mitochondrial fission and clearance in skeletal muscle via the PRKAA/AMPK-PINK1-PRKN/Parkin and PRKAA-DNM1L/DRP1-MFF pathways. Depleting Bdnf expression in myotubes reduced fatty acid-induced mitofission and mitophagy, which was associated with mitochondrial elongation and impaired lipid handling. Muscle-specific bdnf knockout (MBKO) mice displayed defective mitofission and mitophagy, and accumulation of dysfunctional mitochondria in the muscle when they were fed with a high-fat diet (HFD). These animals also have exacerbated body weight gain, increased intramyocellular lipid deposition, reduced energy expenditure, poor metabolic flexibility, and more insulin resistance. In contrast, consuming a BDNF mimetic (7,8-dihydroxyflavone) increased mitochondrial content, and enhanced mitofission and mitophagy in the skeletal muscles. Hence, BDNF is an essential myokine to maintain mitochondrial quality and function, and its repression in obesity might contribute to impaired metabolism.Abbreviation: 7,8-DHF: 7,8-dihydroxyflavone; ACACA/ACC: acetyl Coenzyme A carboxylase alpha; ACAD: acyl-Coenzyme A dehydrogenase family; ACADVL: acyl-Coenzyme A dehydrogenase, very long chain; ACOT: acyl-CoA thioesterase; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2, beta; BDNF: brain derived neurotrophic factor; BNIP3: BCL2/adenovirus E1B interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CCL2/MCP-1: chemokine (C-C motif) ligand 2; CCL5: chemokine (C-C motif) ligand 5; CNS: central nervous system; CPT1B: carnitine palmitoyltransferase 1b, muscle; Cpt2: carnitine palmitoyltransferase 2; CREB: cAMP responsive element binding protein; DNM1L/DRP1: dynamin 1-like; E2: estrogen; EHHADH: enoyl-CoenzymeA hydratase/3-hydroxyacyl CoenzymeA dehydrogenase; ESR1/ER-alpha: estrogen receptor 1 (alpha); FA: fatty acid; FAO: fatty acid oxidation; FCCP: carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone; FFA: free fatty acids; FGF21: fibroblast growth factor 21; FUNDC1: FUN14 domain containing 1; HADHA: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; HFD: high-fat diet; iWAT: inguinal white adipose tissues; MAP1LC3A/LC3A: microtubule-associated protein 1 light chain 3 alpha; MBKO; muscle-specific bdnf knockout; IL6/IL-6: interleukin 6; MCEE: methylmalonyl CoA epimerase; MFF: mitochondrial fission factor; NTRK2/TRKB: neurotrophic tyrosine kinase, receptor, type 2; OPTN: optineurin; PA: palmitic acid; PARL: presenilin associated, rhomboid-like; PDH: pyruvate dehydrogenase; PINK1: PTEN induced putative kinase 1; PPARGC1A/PGC-1α: peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PRKAA/AMPK: protein kinase, AMP-activated, alpha 2 catalytic subunit; ROS: reactive oxygen species; TBK1: TANK-binding kinase 1; TG: triacylglycerides; TNF/TNFα: tumor necrosis factor; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like kinase 1.}, } @article {pmid34685491, year = {2021}, author = {Kurokawa, H and Taninaka, A and Shigekawa, H and Matsui, H}, title = {Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species Production.}, journal = {Cells}, volume = {10}, number = {10}, pages = {}, pmid = {34685491}, issn = {2073-4409}, mesh = {Animals ; Anticoagulants/*pharmacology ; Benzimidazoles/pharmacology ; Dabigatran/*pharmacology ; Epithelial Cells/*drug effects ; Mitochondria/*drug effects ; Rats ; Reactive Oxygen Species/*metabolism ; Thrombin/metabolism ; }, abstract = {Dabigatran is a novel oral anticoagulant that directly inhibits free and fibrin-bound thrombins and exerts rapid and predictable anticoagulant effects. While the use of this reagent has been associated with an increased risk of gastrointestinal bleeding, the reason why dabigatran use increases gastrointestinal bleeding risk remains unknown. We investigated the cytotoxicity of dabigatran etexilate and tartaric acid, the two primary components of dabigatran. The cytotoxicity of dabigatran etexilate and tartaric acid was measured in a cell viability assay. Intracellular mitochondrial reactive oxygen species (mitROS) production and lipid peroxidation were measured using fluorescence dyes. Cell membrane viscosity was measured using atomic force microscopy. The potential of ascorbic acid as an inhibitor of dabigatran cytotoxicity was also evaluated. The cytotoxicity of dabigatran etexilate was higher than that of tartaric acid. Dabigatran etexilate induced mitROS production and lipid peroxidation and altered the cell membrane viscosity. Ascorbic acid inhibited the cytotoxicity and mitROS production induced by dabigatran etexilate. Therefore, we attributed the cytotoxicity of dabigatran to dabigatran etexilate, and proposed that the cytotoxic effects of dabigatran etexilate are mediated via mitROS production. Additionally, we demonstrated that dabigatran cytotoxicity can be prevented via antioxidant treatment.}, } @article {pmid34680141, year = {2021}, author = {Picca, A and Guerra, F and Calvani, R and Romano, R and Coelho-Júnior, HJ and Bucci, C and Marzetti, E}, title = {Mitochondrial Dysfunction, Protein Misfolding and Neuroinflammation in Parkinson's Disease: Roads to Biomarker Discovery.}, journal = {Biomolecules}, volume = {11}, number = {10}, pages = {}, pmid = {34680141}, issn = {2218-273X}, mesh = {Biomarkers/metabolism ; Dopaminergic Neurons/metabolism/pathology ; Humans ; Lewy Bodies/genetics/pathology ; Mitochondria/*genetics/pathology ; Neuroinflammatory Diseases/genetics/pathology ; Parkinson Disease/*genetics/pathology ; Protein Aggregates/genetics ; Proteostasis Deficiencies/*genetics/pathology ; Reactive Oxygen Species/metabolism ; alpha-Synuclein/*genetics ; }, abstract = {Parkinson's Disease (PD) is a highly prevalent neurodegenerative disease among older adults. PD neuropathology is marked by the progressive loss of the dopaminergic neurons of the substantia nigra pars compacta and the widespread accumulation of misfolded intracellular α-synuclein (α-syn). Genetic mutations and post-translational modifications, such as α-syn phosphorylation, have been identified among the multiple factors supporting α-syn accrual during PD. A decline in the clearance capacity of the ubiquitin-proteasome and the autophagy-lysosomal systems, together with mitochondrial dysfunction, have been indicated as major pathophysiological mechanisms of PD neurodegeneration. The accrual of misfolded α-syn aggregates into soluble oligomers, and the generation of insoluble fibrils composing the core of intraneuronal Lewy bodies and Lewy neurites observed during PD neurodegeneration, are ignited by the overproduction of reactive oxygen species (ROS). The ROS activate the α-syn aggregation cascade and, together with the Lewy bodies, promote neurodegeneration. However, the molecular pathways underlying the dynamic evolution of PD remain undeciphered. These gaps in knowledge, together with the clinical heterogeneity of PD, have hampered the identification of the biomarkers that may be used to assist in diagnosis, treatment monitoring, and prognostication. Herein, we illustrate the main pathways involved in PD pathogenesis and discuss their possible exploitation for biomarker discovery.}, } @article {pmid34678674, year = {2021}, author = {Rothmann-Meyer, W and Naidoo, K and de Waal, PJ}, title = {Comparative mitogenomics of Spirocerca lupi from South Africa and China: Variation and possible heteroplasmy.}, journal = {Veterinary parasitology}, volume = {300}, number = {}, pages = {109595}, doi = {10.1016/j.vetpar.2021.109595}, pmid = {34678674}, issn = {1873-2550}, mesh = {Animals ; *Dog Diseases/epidemiology ; Dogs ; Heteroplasmy ; Phylogeny ; South Africa/epidemiology ; *Spirurida Infections/veterinary ; *Thelazioidea/genetics ; }, abstract = {The complete mitochondrial genome of Spirocerca lupi isolated from a dog in South Africa was sequenced using next generation sequencing (NGS) technology and the 12 protein coding genes along with the two rRNA genes were compared to 18 other nematode species as well as S. lupi from China. The mitochondrial genome of S. lupi South Africa had a mean genetic diversity of 6.1 % compared to S. lupi China with some variation in nucleotide composition, gene positioning and size. Pairwise distance results indicated slightly higher variation when compared to the pairwise distances of other closely related species, however, this variation was not high enough for it to be considered a cryptic species. Phylogenetic analysis indicated that S. lupi from the two continents are very similar. In addition, single nucleotide polymorphisms were detected in the nad2 gene with ten sequence variants identified from 10 clones from a single nematode, suggesting possible heteroplasmy. The origin of the heteroplasmy is currently unknown but it is speculated to have arisen from accumulated mutations in the mitochondria during somatic replication.}, } @article {pmid34678428, year = {2022}, author = {Yu, M and Yu, Y and Song, T and Zhang, Y and Wei, F and Cheng, J and Zhang, B and Zhang, X}, title = {Characterization of the voltage-dependent anion channel (VDAC) gene family in wheat (Triticum aestivum L.) and its potential mechanism in response to drought and salinity stresses.}, journal = {Gene}, volume = {809}, number = {}, pages = {146031}, doi = {10.1016/j.gene.2021.146031}, pmid = {34678428}, issn = {1879-0038}, mesh = {Amino Acid Motifs ; Arabidopsis/genetics ; Chromosomes, Plant ; Droughts ; Gene Expression Regulation, Plant ; Multigene Family ; Oxidoreductases/genetics ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic ; Salinity ; Stress, Physiological/*genetics ; Triticum/*genetics/physiology ; Voltage-Dependent Anion Channels/chemistry/*genetics/metabolism ; }, abstract = {Voltage-dependent anion channels (VDACs) are major transport proteins localized in the outer membrane of mitochondria and play critical roles in regulating plant growth and responding to stress. In this study, a total of 26 VDAC genes in common wheat (Triticum aestivum L.) were identified. TaVDACs that contained β-barrel structures were classified into three groups with phylogenetic and sequence alignment. Additionally, the gene structure and protein conserved motif composition varied among diverse subfamilies but were relatively conserved within the same subfamily. The basic elements that were stress- and hormone-related, including TATA-box, CAAT-box, MBS, LTR, TC-rich repeats, ABRE, P-box and TATC-box, were predicted within the promoter region of TaVDAC genes. TaVDAC expression patterns differed among tissues, organs and abiotic stress conditions. Overexpression (OE) of TaVDAC1-B conferred high tolerance to salinity and less resistance to drought stress in Arabidopsis thaliana. TaVDAC1-B interacted with Nucleoredoxin-D1 (TaNRX-D1) protein. Furthermore, compared with WT lines, salinity stress further upregulated the level of AtNRX1 (homologous gene of TaNRX-D1 in Arabidopsis) expression and the activity of superoxide dismutase in TaVDAC1-B OE lines, which led to a decrease in superoxide radical accumulation; drought stress further downregulated AtNRX1 expression and superoxide dismutase activity in TaVDAC1-B OE lines, resulting in the accumulation of superoxide radicals. Our study not only presents comprehensive information for understanding the VDAC gene family in wheat but also proposes a potential mechanism in response to drought and salinity stress.}, } @article {pmid34674637, year = {2021}, author = {Lankheet, I and Vicente, M and Barbieri, C and Schlebusch, C}, title = {The performance of common SNP arrays in assigning African mitochondrial haplogroups.}, journal = {BMC genomic data}, volume = {22}, number = {1}, pages = {43}, pmid = {34674637}, issn = {2730-6844}, mesh = {Black People/*genetics ; DNA, Mitochondrial/*genetics ; Datasets as Topic ; Haplotypes/*genetics ; Humans ; Mitochondria/*genetics ; Oligonucleotide Array Sequence Analysis/*standards ; Polymorphism, Single Nucleotide/*genetics ; Software/standards ; }, abstract = {BACKGROUND: Mitochondrial haplogroup assignment is an important tool for forensics and evolutionary genetics. African populations are known to display a high diversity of mitochondrial haplogroups. In this research we explored mitochondrial haplogroup assignment in African populations using commonly used genome-wide SNP arrays.

RESULTS: We show that, from eight commonly used SNP arrays, two SNP arrays outperform the other arrays when it comes to the correct assignment of African mitochondrial haplogroups. One array enables the recognition of 81% of the African mitochondrial haplogroups from our compiled dataset of full mitochondrial sequences. Other SNP arrays were able to assign 4-62% of the African mitochondrial haplogroups present in our dataset. We also assessed the performance of available software for assigning mitochondrial haplogroups from SNP array data.

CONCLUSIONS: These results provide the first cross-checked quantification of mitochondrial haplogroup assignment performance from SNP array data. Mitochondrial haplogroup frequencies inferred from most common SNP arrays used for human population analysis should be considered with caution.}, } @article {pmid34671161, year = {2021}, author = {Wang, Y and Pedersen, MW and Alsos, IG and De Sanctis, B and Racimo, F and Prohaska, A and Coissac, E and Owens, HL and Merkel, MKF and Fernandez-Guerra, A and Rouillard, A and Lammers, Y and Alberti, A and Denoeud, F and Money, D and Ruter, AH and McColl, H and Larsen, NK and Cherezova, AA and Edwards, ME and Fedorov, GB and Haile, J and Orlando, L and Vinner, L and Korneliussen, TS and Beilman, DW and Bjørk, AA and Cao, J and Dockter, C and Esdale, J and Gusarova, G and Kjeldsen, KK and Mangerud, J and Rasic, JT and Skadhauge, B and Svendsen, JI and Tikhonov, A and Wincker, P and Xing, Y and Zhang, Y and Froese, DG and Rahbek, C and Bravo, DN and Holden, PB and Edwards, NR and Durbin, R and Meltzer, DJ and Kjær, KH and Möller, P and Willerslev, E}, title = {Late Quaternary dynamics of Arctic biota from ancient environmental genomics.}, journal = {Nature}, volume = {600}, number = {7887}, pages = {86-92}, pmid = {34671161}, issn = {1476-4687}, support = {/ERC_/European Research Council/International ; 207492/WT_/Wellcome Trust/United Kingdom ; WT220023/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 069906/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Arctic Regions ; *Biota ; Climate Change/history ; DNA, Ancient/*analysis ; DNA, Environmental/*analysis ; Databases, Genetic ; Datasets as Topic ; Extinction, Biological ; Geologic Sediments ; Grassland ; Greenland ; Haplotypes/genetics ; Herbivory/genetics ; History, Ancient ; Humans ; Lakes ; Mammoths ; *Metagenomics ; Mitochondria/genetics ; Perissodactyla ; Permafrost ; Phylogeny ; Plants/genetics ; Population Dynamics ; Rain ; Siberia ; Spatio-Temporal Analysis ; Wetlands ; }, abstract = {During the last glacial-interglacial cycle, Arctic biotas experienced substantial climatic changes, yet the nature, extent and rate of their responses are not fully understood[1-8]. Here we report a large-scale environmental DNA metagenomic study of ancient plant and mammal communities, analysing 535 permafrost and lake sediment samples from across the Arctic spanning the past 50,000 years. Furthermore, we present 1,541 contemporary plant genome assemblies that were generated as reference sequences. Our study provides several insights into the long-term dynamics of the Arctic biota at the circumpolar and regional scales. Our key findings include: (1) a relatively homogeneous steppe-tundra flora dominated the Arctic during the Last Glacial Maximum, followed by regional divergence of vegetation during the Holocene epoch; (2) certain grazing animals consistently co-occurred in space and time; (3) humans appear to have been a minor factor in driving animal distributions; (4) higher effective precipitation, as well as an increase in the proportion of wetland plants, show negative effects on animal diversity; (5) the persistence of the steppe-tundra vegetation in northern Siberia enabled the late survival of several now-extinct megafauna species, including the woolly mammoth until 3.9 ± 0.2 thousand years ago (ka) and the woolly rhinoceros until 9.8 ± 0.2 ka; and (6) phylogenetic analysis of mammoth environmental DNA reveals a previously unsampled mitochondrial lineage. Our findings highlight the power of ancient environmental metagenomics analyses to advance understanding of population histories and long-term ecological dynamics.}, } @article {pmid34669188, year = {2022}, author = {Fan, Y and Asao, S and Furbank, RT and von Caemmerer, S and Day, DA and Tcherkez, G and Sage, TL and Sage, RF and Atkin, OK}, title = {The crucial roles of mitochondria in supporting C4 photosynthesis.}, journal = {The New phytologist}, volume = {233}, number = {3}, pages = {1083-1096}, doi = {10.1111/nph.17818}, pmid = {34669188}, issn = {1469-8137}, mesh = {Carbon Dioxide/metabolism ; *Malate Dehydrogenase/metabolism ; Mitochondria/metabolism ; *Photosynthesis ; Plant Leaves/physiology ; }, abstract = {C4 photosynthesis involves a series of biochemical and anatomical traits that significantly improve plant productivity under conditions that reduce the efficiency of C3 photosynthesis. We explore how evolution of the three classical biochemical types of C4 photosynthesis (NADP-ME, NAD-ME and PCK types) has affected the functions and properties of mitochondria. Mitochondria in C4 NAD-ME and PCK types play a direct role in decarboxylation of metabolites for C4 photosynthesis. Mitochondria in C4 PCK type also provide ATP for C4 metabolism, although this role for ATP provision is not seen in NAD-ME type. Such involvement has increased mitochondrial abundance/size and associated enzymatic capacity, led to changes in mitochondrial location and ultrastructure, and altered the role of mitochondria in cellular carbon metabolism in the NAD-ME and PCK types. By contrast, these changes in mitochondrial properties are absent in the C4 NADP-ME type and C3 leaves, where mitochondria play no direct role in photosynthesis. From an eco-physiological perspective, rates of leaf respiration in darkness vary considerably among C4 species but does not differ systematically among the three C4 types. This review outlines further mitochondrial research in key areas central to the engineering of the C4 pathway into C3 plants and to the understanding of variation in rates of C4 dark respiration.}, } @article {pmid34662686, year = {2022}, author = {Omeka, WKM and Liyanage, DS and Jeong, T and Lee, S and Lee, J}, title = {Molecular characterization, immune responses, and functional activities of manganese superoxide dismutase in disk abalone (Haliotis discus discus).}, journal = {Developmental and comparative immunology}, volume = {127}, number = {}, pages = {104299}, doi = {10.1016/j.dci.2021.104299}, pmid = {34662686}, issn = {1879-0089}, mesh = {Animals ; *Gastropoda ; Gene Expression Regulation ; Hydrogen Peroxide ; Immunity, Innate ; Mammals ; Phylogeny ; Superoxide Dismutase/genetics ; *Vibrio parahaemolyticus ; }, abstract = {Superoxide dismutases (SODs) are metalloenzymes that convert superoxide radicals to H2O2 and O2. Although SODs have been extensively studied in mammals and other species, comparative studies in invertebrates, such as abalones, are lacking. Here, we aimed to characterize manganese superoxide dismutase in disk abalone (Haliotis discus discus) (AbMnSOD) by assessing its transcriptional levels at different embryonic developmental stages. Additionally, the temporal expression of AbMnSOD in different abalone tissues in response to bacterial, viral, and pathogen-associated molecular pattern (PAMP) stimuli was investigated. SOD activity was measured at various recombinant protein concentrations via the xanthine oxidase/WST-1 system. Cell viability upon exposure to H2O2, wound healing ability, and subcellular localization were determined in AbMnSOD-transfected cells. AbMnSOD was 681 bp long and contained the SOD-A domain. AbMnSOD expression was higher at the trochophore stage than at the other stages. When challenged with immune stimulants, AbMnSOD showed the highest expression at 6 h post-injection (p.i.) for all stimulants except lipopolysaccharides. In the gills, the highest AbMnSOD expression was observed at 6 h p.i., except for the Vibrio parahaemolyticus challenge. Recombinant AbMnSOD showed concentration-dependent xanthine oxidase activity. Furthermore, AbMnSOD-transfected cells survived H2O2-induced apoptosis and exhibited significant wound gap closure. As expected, AbMnSOD was localized in the mitochondria of the cells. Our findings suggest that AbMnSOD is an essential antioxidant enzyme that participates in regulating developmental processes and defense mechanisms against oxidative stress in hosts.}, } @article {pmid34660591, year = {2021}, author = {Lim, HJ and Yoon, H and Kim, H and Kang, YW and Kim, JE and Kim, OY and Lee, EY and Twizere, JC and Rak, J and Kim, DK}, title = {Extracellular Vesicle Proteomes Shed Light on the Evolutionary, Interactive, and Functional Divergence of Their Biogenesis Mechanisms.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {734950}, pmid = {34660591}, issn = {2296-634X}, abstract = {Extracellular vesicles (EVs) are membranous structures containing bioactive molecules, secreted by most cells into the extracellular environment. EVs are classified by their biogenesis mechanisms into two major subtypes: ectosomes (enriched in large EVs; lEVs), budding directly from the plasma membrane, which is common in both prokaryotes and eukaryotes, and exosomes (enriched in small EVs; sEVs) generated through the multivesicular bodies via the endomembrane system, which is unique to eukaryotes. Even though recent proteomic analyses have identified key proteins associated with EV subtypes, there has been no systematic analysis, thus far, to support the general validity and utility of current EV subtype separation methods, still largely dependent on physical properties, such as vesicular size and sedimentation. Here, we classified human EV proteomic datasets into two main categories based on distinct centrifugation protocols commonly used for isolating sEV or lEV fractions. We found characteristic, evolutionarily conserved profiles of sEV and lEV proteins linked to their respective biogenetic origins. This may suggest that the evolutionary trajectory of vesicular proteins may result in a membership bias toward specific EV subtypes. Protein-protein interaction (PPI) network analysis showed that vesicular proteins formed distinct clusters with proteins in the same EV fraction, providing evidence for the existence of EV subtype-specific protein recruiters. Moreover, we identified functional modules enriched in each fraction, including multivesicular body sorting for sEV, and mitochondria cellular respiration for lEV proteins. Our analysis successfully captured novel features of EVs embedded in heterogeneous proteomics studies and suggests specific protein markers and signatures to be used as quality controllers in the isolation procedure for subtype-enriched EV fractions.}, } @article {pmid34655689, year = {2022}, author = {do Amaral, MJ and de Andrade Rosa, I and Andrade, SA and Fang, X and Andrade, LR and Costa, ML and Mermelstein, C}, title = {The perinuclear region concentrates disordered proteins with predicted phase separation distributed in a 3D network of cytoskeletal filaments and organelles.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1869}, number = {1}, pages = {119161}, pmid = {34655689}, issn = {1879-2596}, support = {R00 HL143210/HL/NHLBI NIH HHS/United States ; R01 HL157115/HL/NHLBI NIH HHS/United States ; R01 HL158761/HL/NHLBI NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/genetics/*metabolism/ultrastructure ; Animals ; Cells, Cultured ; Chick Embryo ; Intrinsically Disordered Proteins/metabolism ; Lysosomes/metabolism/ultrastructure ; Microscopy, Electron, Transmission/methods ; Mitochondria/metabolism/ultrastructure ; Nuclear Envelope/*metabolism/ultrastructure ; Proteome/genetics/metabolism ; Zebrafish ; }, abstract = {Membraneless organelles have emerged during the evolution of eukaryotic cells as intracellular domains in which multiple proteins organize into complex structures to perform specialized functions without the need of a lipid bilayer compartment. Here we describe the perinuclear space of eukaryotic cells as a highly organized network of cytoskeletal filaments that facilitates assembly of biomolecular condensates. Using bioinformatic analyses, we show that the perinuclear proteome is enriched in intrinsic disorder with several proteins predicted to undergo liquid-liquid phase separation. We also analyze immunofluorescence and transmission electron microscopy images showing the association between the nucleus and other organelles, such as mitochondria and lysosomes, or the labeling of specific proteins within the perinuclear region of cells. Altogether our data support the existence of a perinuclear dense sub-micron region formed by a well-organized three-dimensional network of structural and signaling proteins, including several proteins containing intrinsically disordered regions with phase behavior. This network of filamentous cytoskeletal proteins extends a few micrometers from the nucleus, contributes to local crowding, and organizes the movement of molecular complexes within the perinuclear space. Our findings take a key step towards understanding how membraneless regions within eukaryotic cells can serve as hubs for biomolecular condensates assembly, in particular the perinuclear space. Finally, evaluation of the disease context of the perinuclear proteins revealed that alterations in their expression can lead to several pathological conditions, and neurological disorders and cancer are among the most frequent.}, } @article {pmid34645790, year = {2021}, author = {Frye, RE and Lionnard, L and Singh, I and Karim, MA and Chajra, H and Frechet, M and Kissa, K and Racine, V and Ammanamanchi, A and McCarty, PJ and Delhey, L and Tippett, M and Rose, S and Aouacheria, A}, title = {Mitochondrial morphology is associated with respiratory chain uncoupling in autism spectrum disorder.}, journal = {Translational psychiatry}, volume = {11}, number = {1}, pages = {527}, pmid = {34645790}, issn = {2158-3188}, mesh = {*Autism Spectrum Disorder/metabolism ; Electron Transport ; Electron Transport Complex I ; Humans ; Mitochondria/metabolism ; Oxidation-Reduction ; }, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is associated with unique changes in mitochondrial metabolism, including elevated respiration rates and morphological alterations. We examined electron transport chain (ETC) complex activity in fibroblasts derived from 18 children with ASD as well as mitochondrial morphology measurements in fibroblasts derived from the ASD participants and four typically developing controls. In ASD participants, symptoms severity was measured by the Social Responsiveness Scale and Aberrant Behavior Checklist. Mixed-model regression demonstrated that alterations in mitochondrial morphology were associated with both ETC Complex I+III and IV activity as well as the difference between ETC Complex I+III and IV activity. The subgroup of ASD participants with relative elevation in Complex IV activity demonstrated more typical mitochondrial morphology and milder ASD related symptoms. This study is limited by sample size given the invasive nature of obtaining fibroblasts from children. Furthermore, since mitochondrial function is heterogenous across tissues, the result may be specific to fibroblast respiration. Previous studies have separately described elevated ETC Complex IV activity and changes in mitochondrial morphology in cells derived from children with ASD but this is the first study to link these two findings in mitochondrial metabolism. The association between a difference in ETC complex I+III and IV activity and normal morphology suggests that mitochondrial in individuals with ASD may require ETC uncoupling to function optimally. Further studies should assess the molecular mechanisms behind these unique metabolic changes.Trial registration: Protocols used in this study were registered in clinicaltrials.gov as NCT02000284 and NCT02003170.}, } @article {pmid34644400, year = {2021}, author = {Szoke, T and Nussbaum-Shochat, A and Amster-Choder, O}, title = {Evolutionarily conserved mechanism for membrane recognition from bacteria to mitochondria.}, journal = {FEBS letters}, volume = {595}, number = {22}, pages = {2805-2815}, doi = {10.1002/1873-3468.14203}, pmid = {34644400}, issn = {1873-3468}, mesh = {*Conserved Sequence ; Escherichia coli ; Escherichia coli Proteins/chemistry/*genetics/metabolism ; *Evolution, Molecular ; Membrane Proteins/chemistry/*genetics/metabolism ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/chemistry/*genetics/metabolism ; Protein Domains ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins/chemistry/*genetics/metabolism ; }, abstract = {The mechanisms controlling membrane recognition by proteins with one hydrophobic stretch at their carboxyl terminus (tail anchor, TA) are poorly defined. The Escherichia coli TAs of ElaB and YqjD, which share sequential and structural similarity with the Saccharomyces cerevisiae TA of Fis1, were shown to localize to mitochondria. We show that YqjD and ElaB are directed by their TAs to bacterial cell poles. Fis1(TA) expressed in E. coli localizes like the endogenous TAs. The yeast and bacterial TAs are inserted in the E. coli inner membrane, and they all show affiliation to phosphatidic acid (PA), found in the membrane of the bacterial cell poles and of the yeast mitochondria. Our results suggest a mechanism for TA membrane recognition conserved from bacteria to mitochondria and raise the possibility that through their interaction with PA, and TAs play a role across prokaryotes and eukaryotes in controlling cell/organelle fate.}, } @article {pmid34643951, year = {2022}, author = {Adriano, EA and Zatti, SA and Okamura, B}, title = {How to build single-celled cnidarians with worm-like motility: Lessons from Myxozoa.}, journal = {Journal of anatomy}, volume = {240}, number = {3}, pages = {475-488}, pmid = {34643951}, issn = {1469-7580}, mesh = {Animals ; *Cnidaria ; *Fish Diseases/parasitology ; Gallbladder ; *Myxozoa/physiology/ultrastructure ; Phylogeny ; }, abstract = {Metazoans with worm-like morphologies across diverse and disparate groups typically demonstrate motility generated by hydrostatic skeletons involving tissue layers (muscles and epithelia). Here we present representative morphological, behavioural and molecular data for parasitic cnidarians (myxozoans) that demonstrate unprecedented variation in form and function, developing as cellular hydrostats. Motile elongate plasmodia characterise a remarkable radiation of species in the genus Ceratomyxa. The vermiform plasmodia inhabit gall bladders of a range of South American freshwater fish and exhibit undulatory motility reminiscent of nematodes but achieved at the cellular level. Collective insights from ultrastructure, confocal and light microscopy along with videos depicting movements highlight key features that we propose explain the unique motility of the plasmodia. These features include cytoskeletal elements (net forming microfilaments and microtubules), a large internal vacuole, a relatively rigid outer glycocalyx and peripherally arranged mitochondria. These constituents provide collective evidence for repurposing of the cnidarian epitheliomuscular cell to support worm-like motility at the cellular level. The apparent restriction of vermiform ceratomyxids to South American freshwaters suggests an origination via Cretaceous or Miocene marine transgressions and subsequent radiation.}, } @article {pmid34633451, year = {2022}, author = {Valera-Calero, JA and Úbeda-D'Ocasar, E and Caballero-Corella, M and Fernández-de-Las-Peñas, C and Sendarrubias, GMG and Arias-Buría, JL}, title = {Cervical Multifidus Morphology and Quality Are Not Associated with Clinical Variables in Women with Fibromyalgia: An Observational Study.}, journal = {Pain medicine (Malden, Mass.)}, volume = {23}, number = {6}, pages = {1138-1143}, doi = {10.1093/pm/pnab297}, pmid = {34633451}, issn = {1526-4637}, mesh = {Cervical Vertebrae/diagnostic imaging ; Female ; *Fibromyalgia/diagnostic imaging ; Humans ; Neck ; Pain ; *Paraspinal Muscles ; }, abstract = {OBJECTIVE: Some studies have reported the presence of histological alterations, such as myofiber disorganization and abnormalities in the number and shape of mitochondria, in patients with fibromyalgia syndrome (FMS). Although Ultrasound imaging (US) is used to quantitatively characterize muscle tissues, US studies in patients with FMS are lacking. Therefore, we aimed to describe morphological and qualitative cervical multifidus (CM) muscle US features in women with FMS and to assess their correlation with clinical indicators.

DESIGN: Observational study.

SETTING: AFINSYFACRO Fibromyalgia Association (Madrid, Spain).

SUBJECTS: Forty-five women with FMS participated.

METHODS: Sociodemographic variables (e.g., age, height, weight, body mass index) and clinical outcomes (e.g., pain as assessed on a numerical pain rating scale, evolution time, pain-related disability as assessed by the Fibromyalgia Impact Questionnaire) were collected. Images were acquired bilaterally at the cervical spine (C4-C5 level) and measured by an experienced examiner for assessment of muscle morphology (e.g., cross-sectional area, perimeter, and shape) and quality (mean echo intensity and intramuscular fatty infiltration). Side-to-side comparisons and a correlational analysis were conducted.

RESULTS: No significant side-to-side differences were found for morphology or quality features (P > 0.05). None of the clinical indicators were associated with US characteristics (all, P > 0.05).

CONCLUSION: Our results showed no side-to-side differences for CM morphology and quality as assessed with US. No associations between CM muscle morphology or quality and Fibromyalgia Impact Questionnaire, pressure pain threshold, numerical pain rating scale score, or evolution time were observed. Our preliminary data suggest that muscle morphology is not directly related to pain and pain-related disability in women with FMS.}, } @article {pmid34626646, year = {2021}, author = {Latimer, S and Keene, SA and Stutts, LR and Berger, A and Bernert, AC and Soubeyrand, E and Wright, J and Clarke, CF and Block, AK and Colquhoun, TA and Elowsky, C and Christensen, A and Wilson, MA and Basset, GJ}, title = {A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in Arabidopsis.}, journal = {The Journal of biological chemistry}, volume = {297}, number = {5}, pages = {101283}, pmid = {34626646}, issn = {1083-351X}, support = {R01 GM139978/GM/NIGMS NIH HHS/United States ; RF1 AG061566/AG/NIA NIH HHS/United States ; }, mesh = {*Arabidopsis/enzymology/genetics ; *Arabidopsis Proteins/genetics/metabolism ; *Mitochondria/enzymology/genetics ; *Mixed Function Oxygenases/genetics/metabolism ; *Phylogeny ; *Ubiquinone/genetics/metabolism ; }, abstract = {Ubiquinone (Coenzyme Q) is a vital respiratory cofactor and liposoluble antioxidant. In plants, it is not known how the C-6 hydroxylation of demethoxyubiquinone, the penultimate step in ubiquinone biosynthesis, is catalyzed. The combination of cross-species gene network modeling along with mining of embryo-defective mutant databases of Arabidopsis thaliana identified the embryo lethal locus EMB2421 (At1g24340) as a top candidate for the missing plant demethoxyubiquinone hydroxylase. In marked contrast with prototypical eukaryotic demethoxyubiquinone hydroxylases, the catalytic mechanism of which depends on a carboxylate-bridged di-iron domain, At1g24340 is homologous to FAD-dependent oxidoreductases that instead use NAD(P)H as an electron donor. Complementation assays in Saccharomyces cerevisiae and Escherichia coli demonstrated that At1g24340 encodes a functional demethoxyubiquinone hydroxylase and that the enzyme displays strict specificity for the C-6 position of the benzoquinone ring. Laser-scanning confocal microscopy also showed that GFP-tagged At1g24340 is targeted to mitochondria. Silencing of At1g24340 resulted in 40 to 74% decrease in ubiquinone content and de novo ubiquinone biosynthesis. Consistent with the role of At1g24340 as a benzenoid ring modification enzyme, this metabolic blockage could not be bypassed by supplementation with 4-hydroxybenzoate, the immediate precursor of ubiquinone's ring. Unlike in yeast, in Arabidopsis overexpression of demethoxyubiquinone hydroxylase did not boost ubiquinone content. Phylogenetic reconstructions indicated that plant demethoxyubiquinone hydroxylase is most closely related to prokaryotic monooxygenases that act on halogenated aromatics and likely descends from an event of horizontal gene transfer between a green alga and a bacterium.}, } @article {pmid34618964, year = {2020}, author = {Soto Gomez, M and Lin, Q and da Silva Leal, E and Gallaher, TJ and Scherberich, D and Mennes, CB and Smith, SY and Graham, SW}, title = {A bi-organellar phylogenomic study of Pandanales: inference of higher-order relationships and unusual rate-variation patterns.}, journal = {Cladistics : the international journal of the Willi Hennig Society}, volume = {36}, number = {5}, pages = {481-504}, doi = {10.1111/cla.12417}, pmid = {34618964}, issn = {1096-0031}, mesh = {Genes, Plant ; *Genome, Mitochondrial ; *Genome, Plastid ; Magnoliopsida/*classification/*genetics ; Mitochondria/genetics ; Phylogeny ; Plastids/genetics ; }, abstract = {We used a bi-organellar phylogenomic approach to address higher-order relationships in Pandanales, including the first molecular phylogenetic study of the panama-hat family, Cyclanthaceae. Our genus-level study of plastid and mitochondrial gene sets includes a comprehensive sampling of photosynthetic lineages across the order, and provides a framework for investigating clade ages, biogeographic hypotheses and organellar molecular evolution. Using multiple inference methods and both organellar genomes, we recovered mostly congruent and strongly supported relationships within and between families, including the placement of fully mycoheterotrophic Triuridaceae. Cyclanthaceae and Pandanaceae plastomes have slow substitution rates, contributing to weakly supported plastid-based relationships in Cyclanthaceae. While generally slowly evolving, mitochondrial genomes exhibit sporadic rate elevation across the order. However, we infer well-supported relationships even for slower evolving mitochondrial lineages in Cyclanthaceae. Clade age estimates across photosynthetic lineages are largely consistent with previous studies, are well correlated between the two organellar genomes (with slightly younger inferences from mitochondrial data), and support several biogeographic hypotheses. We show that rapidly evolving non-photosynthetic lineages may bias age estimates upwards at neighbouring photosynthetic nodes, even using a relaxed clock model. Finally, we uncovered new genome structural variants in photosynthetic taxa at plastid inverted repeat boundaries that show promise as interfamilial phylogenetic markers.}, } @article {pmid34616376, year = {2021}, author = {Lin, R and Xia, Y and Liu, Y and Zhang, D and Xiang, X and Niu, X and Jiang, L and Wang, X and Zheng, A}, title = {Comparative Mitogenomic Analysis and the Evolution of Rhizoctonia solani Anastomosis Groups.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {707281}, pmid = {34616376}, issn = {1664-302X}, abstract = {Mitochondria are the major energy source for cell functions. However, for the plant fungal pathogens, mitogenome variations and their roles during the host infection processes remain largely unknown. Rhizoctonia solani, an important soil-borne pathogen, forms different anastomosis groups (AGs) and adapts to a broad range of hosts in nature. Here, we reported three complete mitogenomes of AG1-IA RSIA1, AG1-IB RSIB1, and AG1-IC, and performed a comparative analysis with nine published Rhizoctonia mitogenomes (AG1-IA XN, AG1-IB 7/3/14, AG3, AG4, and five Rhizoctonia sp. mitogenomes). These mitogenomes encoded 15 typical proteins (cox1-3, cob, atp6, atp8-9, nad1-6, nad4L, and rps3) and several LAGLIDADG/GIY-YIG endonucleases with sizes ranging from 109,017 bp (Rhizoctonia sp. SM) to 235,849 bp (AG3). We found that their large sizes were mainly contributed by repeat sequences and genes encoding endonucleases. We identified the complete sequence of the rps3 gene in 10 Rhizoctonia mitogenomes, which contained 14 positively selected sites. Moreover, we inferred a robust maximum-likelihood phylogeny of 32 Basidiomycota mitogenomes, representing that seven R. solani and other five Rhizoctonia sp. lineages formed two parallel branches in Agaricomycotina. The comparative analysis showed that mitogenomes of Basidiomycota pathogens had high GC content and mitogenomes of R. solani had high repeat content. Compared to other strains, the AG1-IC strain had low substitution rates, which may affect its mitochondrial phylogenetic placement in the R. solani clade. Additionally, with the published RNA-seq data, we investigated gene expression patterns from different AGs during host infection stages. The expressed genes from AG1-IA (host: rice) and AG3 (host: potato) mainly formed four groups by k-mean partitioning analysis. However, conserved genes represented varied expression patterns, and only the patterns of rps3-nad2 and nad1-m3g18/mag28 (an LAGLIDADG endonuclease) were conserved in AG1-IA and AG3 as shown by the correlation coefficient analysis, suggesting regulation of gene repertoires adapting to infect varied hosts. The results of variations in mitogenome characteristics and the gene substitution rates and expression patterns may provide insights into the evolution of R. solani mitogenomes.}, } @article {pmid34614167, year = {2021}, author = {Sanchez-Contreras, M and Sweetwyne, MT and Kohrn, BF and Tsantilas, KA and Hipp, MJ and Schmidt, EK and Fredrickson, J and Whitson, JA and Campbell, MD and Rabinovitch, PS and Marcinek, DJ and Kennedy, SR}, title = {A replication-linked mutational gradient drives somatic mutation accumulation and influences germline polymorphisms and genome composition in mitochondrial DNA.}, journal = {Nucleic acids research}, volume = {49}, number = {19}, pages = {11103-11118}, pmid = {34614167}, issn = {1362-4962}, support = {T32 AG066574/AG/NIA NIH HHS/United States ; T32 AG000057/AG/NIA NIH HHS/United States ; R21 HG011229/HG/NHGRI NIH HHS/United States ; R21 DK128540/DK/NIDDK NIH HHS/United States ; K01 AG062757/AG/NIA NIH HHS/United States ; R21 CA259780/CA/NCI NIH HHS/United States ; P01 AG001751/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*genetics/metabolism ; Animals ; Chromosome Mapping ; DNA Polymerase gamma/deficiency/genetics ; *DNA Replication ; DNA, Mitochondrial/*genetics/metabolism ; Genetic Speciation ; *Genome, Mitochondrial ; *Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/*genetics/metabolism ; *Mutation Accumulation ; Mutation Rate ; Polymorphism, Single Nucleotide ; }, abstract = {Mutations in mitochondrial DNA (mtDNA) cause maternally inherited diseases, while somatic mutations are linked to common diseases of aging. Although mtDNA mutations impact health, the processes that give rise to them are under considerable debate. To investigate the mechanism by which de novo mutations arise, we analyzed the distribution of naturally occurring somatic mutations across the mouse and human mtDNA obtained by Duplex Sequencing. We observe distinct mutational gradients in G→A and T→C transitions delimited by the light-strand origin and the mitochondrial Control Region (mCR). The gradient increases unequally across the mtDNA with age and is lost in the absence of DNA polymerase γ proofreading activity. In addition, high-resolution analysis of the mCR shows that important regulatory elements exhibit considerable variability in mutation frequency, consistent with them being mutational 'hot-spots' or 'cold-spots'. Collectively, these patterns support genome replication via a deamination prone asymmetric strand-displacement mechanism as the fundamental driver of mutagenesis in mammalian DNA. Moreover, the distribution of mtDNA single nucleotide polymorphisms in humans and the distribution of bases in the mtDNA across vertebrate species mirror this gradient, indicating that replication-linked mutations are likely the primary source of inherited polymorphisms that, over evolutionary timescales, influences genome composition during speciation.}, } @article {pmid34610767, year = {2021}, author = {Evans, BJ and Peter, BM and Melnick, DJ and Andayani, N and Supriatna, J and Zhu, J and Tosi, AJ}, title = {Mitonuclear interactions and introgression genomics of macaque monkeys (Macaca) highlight the influence of behaviour on genome evolution.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1960}, pages = {20211756}, pmid = {34610767}, issn = {1471-2954}, mesh = {Animals ; Evolution, Molecular ; Female ; *Genome, Mitochondrial ; Genomics ; Haplorhini ; *Macaca/genetics ; Male ; }, abstract = {In most macaques, females are philopatric and males migrate from their natal ranges, which results in pronounced divergence of mitochondrial genomes within and among species. We therefore predicted that some nuclear genes would have to acquire compensatory mutations to preserve compatibility with diverged interaction partners from the mitochondria. We additionally expected that these sex-differences would have distinctive effects on gene flow in the X and autosomes. Using new genomic data from 29 individuals from eight species of Southeast Asian macaque, we identified evidence of natural selection associated with mitonuclear interactions, including extreme outliers of interspecies differentiation and metrics of positive selection, low intraspecies polymorphism and atypically long runs of homozygosity associated with nuclear-encoded genes that interact with mitochondria-encoded genes. In one individual with introgressed mitochondria, we detected a small but significant enrichment of autosomal introgression blocks from the source species of her mitochondria that contained genes which interact with mitochondria-encoded loci. Our analyses also demonstrate that sex-specific demography sculpts genetic exchange across multiple species boundaries. These findings show that behaviour can have profound but indirect effects on genome evolution by influencing how interacting components of different genomic compartments (mitochondria, the autosomes and the sex chromosomes) move through time and space.}, } @article {pmid34603395, year = {2021}, author = {Rodríguez, E and Grover Thomas, F and Camus, MF and Lane, N}, title = {Mitonuclear Interactions Produce Diverging Responses to Mild Stress in Drosophila Larvae.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {734255}, pmid = {34603395}, issn = {1664-8021}, abstract = {Mitochondrial function depends on direct interactions between respiratory proteins encoded by genes in two genomes, mitochondrial and nuclear, which evolve in very different ways. Serious incompatibilities between these genomes can have severe effects on development, fitness and viability. The effect of subtle mitonuclear mismatches has received less attention, especially when subject to mild physiological stress. Here, we investigate how two distinct physiological stresses, metabolic stress (high-protein diet) and redox stress [the glutathione precursor N-acetyl cysteine (NAC)], affect development time, egg-to-adult viability, and the mitochondrial physiology of Drosophila larvae with an isogenic nuclear background set against three mitochondrial DNA (mtDNA) haplotypes: one coevolved (WT) and two slightly mismatched (COX and BAR). Larvae fed the high-protein diet developed faster and had greater viability in all haplotypes. The opposite was true of NAC-fed flies, especially those with the COX haplotype. Unexpectedly, the slightly mismatched BAR larvae developed fastest and were the most viable on both treatments, as well as control diets. These changes in larval development were linked to a shift to complex I-driven mitochondrial respiration in all haplotypes on the high-protein diet. In contrast, NAC increased respiration in COX larvae but drove a shift toward oxidation of proline and succinate. The flux of reactive oxygen species was increased in COX larvae treated with NAC and was associated with an increase in mtDNA copy number. Our results support the notion that subtle mitonuclear mismatches can lead to diverging responses to mild physiological stress, undermining fitness in some cases, but surprisingly improving outcomes in other ostensibly mismatched fly lines.}, } @article {pmid34600156, year = {2021}, author = {Sahebnasagh, A and Hashemi, J and Khoshi, A and Saghafi, F and Avan, R and Faramarzi, F and Azimi, S and Habtemariam, S