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Bibliography on: Mitochondrial Evolution

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ESP: PubMed Auto Bibliography 08 Aug 2022 at 01:43 Created: 

Mitochondrial Evolution

The endosymbiotic hypothesis for the origin of mitochondria (and chloroplasts) suggests that mitochondria are descended from specialized bacteria (probably purple nonsulfur bacteria) that somehow survived endocytosis by another species of prokaryote or some other cell type, and became incorporated into the cytoplasm.

Created with PubMed® Query: mitochondria AND evolution NOT 26799652[PMID] NOT 33634751[PMID] NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2022-08-04
CmpDate: 2022-08-04

Liu Q, Iqbal MF, Yaqub T, et al (2022)

The transmission of human mitochondrial DNA in four-generation pedigrees.

Human mutation, 43(9):1259-1267.

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.

RevDate: 2022-08-03

Liao T, Wang S, Stüeken EE, et al (2022)

Phylogenomic evidence for the Origin of Obligately Anaerobic Anammox Bacteria around the Great Oxidation Event.

Molecular biology and evolution pii:6653777 [Epub ahead of print].

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, remains enigmatic. Here, we performed comprehensive phylogenomic and molecular clock analysis of anammox bacteria within the phylum Planctomycetes. After accommodating the uncertainties and factors influencing time estimates, which includes 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 to 2.5 billion years ago [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.

RevDate: 2022-08-03

Paulino MG, Rossi PA, Venturini FP, et al (2022)

Liver dysfunction and energy storage mobilization in traíra, Hoplias malabaricus (Teleostei, Erythrinidae) induced by subchronic exposure to toxic cyanobacterial crude extract.

Environmental toxicology [Epub ahead of print].

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.

RevDate: 2022-08-01

Schavemaker PE, SA Muñoz-Gómez (2022)

The role of mitochondrial energetics in the origin and diversification of eukaryotes.

Nature ecology & evolution [Epub ahead of print].

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 100‒103 µm3, the genomic architecture of extant eukaryotes is only slightly advantageous at genomes sizes of 106‒107 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.

RevDate: 2022-08-01

Yu J, Ran Z, Zhang J, et al (2022)

Genome-Wide Insights Into the Organelle Translocation of Photosynthetic NDH-1 Genes During Evolution.

Frontiers in microbiology, 13:956578.

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.

RevDate: 2022-08-01

Mondal S, Kinatukara P, Singh S, et al (2022)

DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes.

eLife, 11: pii:77665.

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.

RevDate: 2022-07-28

Pani P, NC Bal (2022)

Avian adjustments to cold and non-shivering thermogenesis: whats, wheres and hows.

Biological reviews of the Cambridge Philosophical Society [Epub ahead of print].

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 Ca2+ -ATPase (SERCA) and ryanodine receptor 1 (RyR1) are key in avian muscle NST, through their mediation of futile Ca2+ 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. Ca2+ signalling in the muscle seems to be common to contraction, shivering and NST, but elucidating its roles will require more precise measurement of local Ca2+ 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.

RevDate: 2022-07-28
CmpDate: 2022-07-28

Tao J, Li B, Cheng J, et al (2022)

Genomic Divergence Characterization and Quantitative Proteomics Exploration of Type 4 Porcine Astrovirus.

Viruses, 14(7): pii:v14071383.

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.

RevDate: 2022-07-27

Atayik MC, U Çakatay (2022)

Melatonin-related signaling pathways and their regulatory effects in aging organisms.

Biogerontology [Epub ahead of print].

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.

RevDate: 2022-07-27

Ghanem J, Passadori A, Severac F, et al (2022)

Effects of Rehabilitation on Long-COVID-19 Patient's Autonomy, Symptoms and Nutritional Observance.

Nutrients, 14(15): pii:nu14153027.

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.

RevDate: 2022-07-27

Mendoza-Hoffmann F, Zarco-Zavala M, Ortega R, et al (2022)

Evolution of the Inhibitory and Non-Inhibitory ε, ζ, and IF1 Subunits of the F1FO-ATPase as Related to the Endosymbiotic Origin of Mitochondria.

Microorganisms, 10(7): pii:microorganisms10071372.

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.

RevDate: 2022-07-27

Shang Y, Wang X, Liu G, et al (2022)

Adaptability and Evolution of Gobiidae: A Genetic Exploration.

Animals : an open access journal from MDPI, 12(14): pii:ani12141741.

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.

RevDate: 2022-07-27
CmpDate: 2022-07-27

Ge H, Xu J, Hua M, et al (2022)

Genome-wide identification and analysis of ACP gene family in Sorghum bicolor (L.) Moench.

BMC genomics, 23(1):538.

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.

RevDate: 2022-07-25

Wu CS, SM Chaw (2022)

Evolution of mitochondrial RNA editing in extant gymnosperms.

The Plant journal : for cell and molecular biology [Epub ahead of print].

To unveil the evolution of mitochondrial RNA editing in gymnosperms, we characterized mitogenomes, plastomes, RNA editing sites, and pentatricopeptide repeat (PPR) proteins from ten 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 highest expressed genes involved in the respiratory complex. We identified 9,132 mitochondrial C-to-U editing sites, as well as 2,846 P-class and 8,530 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 nonsynonymous 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 nonsynonymous 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 RRP 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.

RevDate: 2022-07-25

Ebner JN, Wyss MK, Ritz D, et al (2022)

Effects of thermal acclimation on the proteome of the planarian Crenobia alpina from an alpine freshwater spring.

The Journal of experimental biology pii:276068 [Epub ahead of print].

Species' acclimation capacities and their ability to maintain molecular homeostasis outside of 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 plasticities, and that these species may be particularly vulnerable to temperature increase. Whether such species retained or lost acclimation capacities 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 cold-adapted stenotherm. We found that the species' CTmax is above its experienced habitat temperatures and that different populations exhibit differential CTmax acclimation capacities, 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 a comprehensively annotated species-specific proteome. Network analyses of 3399 proteins and protein set enrichment show 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 abundant following warm acclimation. Proteins associated with an unfolded protein response, ciliogenesis, tissue damage repair, development, and the innate immune system were higher abundant 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 retained plasticity in response to elevated temperatures, challenging the notion that stable environments necessarily result in muted plasticity.

RevDate: 2022-07-23

Visinoni F, D Delneri (2022)

Mitonuclear interplay in yeast: from speciation to phenotypic adaptation.

Current opinion in genetics & development, 76:101957 pii:S0959-437X(22)00066-1 [Epub ahead of print].

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.

RevDate: 2022-07-25
CmpDate: 2022-07-25

Cadart C, R Heald (2022)

Scaling of biosynthesis and metabolism with cell size.

Molecular biology of the cell, 33(9):pe5.

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.

RevDate: 2022-07-22

McCall CE, Zhu X, Zabalawi M, et al (2022)

Sepsis, pyruvate, and mitochondria energy supply chain shortage.

Journal of leukocyte biology [Epub ahead of print].

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.

RevDate: 2022-07-20

Brzęk P, Roussel D, M Konarzewski (2022)

Mice selected for a high basal metabolic rate evolved larger guts but not more efficient mitochondria.

Proceedings. Biological sciences, 289(1978):20220719.

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.

RevDate: 2022-07-21
CmpDate: 2022-07-21

Carter CS, MA Kingsbury (2022)

Oxytocin and oxygen: the evolution of a solution to the 'stress of life'.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 377(1858):20210054.

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'.

RevDate: 2022-07-19

Rottenberg H (2022)

The accelerated evolution of human cytochrome c oxidase - Selection for reduced rate and proton pumping efficiency?.

Biochimica et biophysica acta. Bioenergetics pii:S0005-2728(22)00064-0 [Epub ahead of print].

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.

RevDate: 2022-07-15

Shen LL, Waheed A, Wang YP, et al (2022)

Mitochondrial Genome Contributes to the Thermal Adaptation of the Oomycete Phytophthora infestans.

Frontiers in microbiology, 13:928464.

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.

RevDate: 2022-07-13
CmpDate: 2022-07-13

Vella A, Vella N, C Acosta-Díaz (2022)

The first complete mitochondrial genomes for Serranus papilionaceus and Serranus scriba, and their phylogenetic position within Serranidae.

Molecular biology reports, 49(7):6295-6302.

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.

RevDate: 2022-07-09

Bononi G, Masoni S, Di Bussolo V, et al (2022)

Historical perspective of tumor glycolysis: a century with Otto Warburg.

Seminars in cancer biology pii:S1044-579X(22)00162-6 [Epub ahead of print].

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.

RevDate: 2022-07-08
CmpDate: 2022-07-08

Gumińska N, R Milanowski (2022)

Types of circular DNA in Eukarya.

Postepy biochemii, 68(2):129-141.

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.

RevDate: 2022-07-05

Savu DI, N Moisoi (2022)

Mitochondria - Nucleus communication in neurodegenerative disease. Who talks first, who talks louder?.

Biochimica et biophysica acta. Bioenergetics pii:S0005-2728(22)00057-3 [Epub ahead of print].

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.

RevDate: 2022-07-01

Jardim-Messeder D, Zamocky M, Sachetto-Martins G, et al (2022)

Chloroplastic Ascorbate Peroxidases Targeted to Stroma or Thylakoid membrane: The Chicken or Egg Dilemma.

FEBS letters [Epub ahead of print].

Ascorbate peroxidases (APXs) are heme peroxidases that remove hydrogen peroxide in different subcellular compartments with concomitant ascorbate cycling. Here, we analyzed 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 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.

RevDate: 2022-06-28

Anderson L, Camus MF, Monteith KM, et al (2022)

Variation in mitochondrial DNA affects locomotor activity and sleep in Drosophila melanogaster.

Heredity [Epub ahead of print].

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.

RevDate: 2022-06-30
CmpDate: 2022-06-30

Jenkins HL, Graham R, Porter JS, et al (2022)

Unprecedented frequency of mitochondrial introns in colonial bilaterians.

Scientific reports, 12(1):10889.

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.

RevDate: 2022-06-27

Garrido C, Wollman FA, I Lafontaine (2022)

The evolutionary history of peptidases involved in the processing of Organelle-Targeting Peptides.

Genome biology and evolution pii:6618273 [Epub ahead of print].

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 MPP, SPP, PreP and OOP peptidases 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.

RevDate: 2022-06-27
CmpDate: 2022-06-27

Ždralević M, S Giannattasio (2022)

Mitochondrial Research: Yeast and Human Cells as Models.

International journal of molecular sciences, 23(12): pii:ijms23126654.

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 [...].

RevDate: 2022-06-27
CmpDate: 2022-06-27

Solana JC, Chicharro C, García E, et al (2022)

Assembly of a Large Collection of Maxicircle Sequences and Their Usefulness for Leishmania Taxonomy and Strain Typing.

Genes, 13(6): pii:genes13061070.

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.

RevDate: 2022-06-27
CmpDate: 2022-06-27

Hawkins MTR, Bailey CA, Brown AM, et al (2022)

Nuclear and Mitochondrial Phylogenomics of the Sifakas Reveal Cryptic Variation in the Diademed Sifaka.

Genes, 13(6): pii:genes13061026.

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 km2). 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.

RevDate: 2022-06-27
CmpDate: 2022-06-27

Orlova VF, Solovyeva EN, Dunayev EA, et al (2022)

Integrative Taxonomy within Eremias multiocellata Complex (Sauria, Lacertidae) from the Western Part of Range: Evidence from Historical DNA.

Genes, 13(6): pii:genes13060941.

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.

RevDate: 2022-06-24

Martínez-González JJ, Guevara-Flores A, IP Del Arenal Mena (2022)

Evolutionary Adaptations of Parasitic Flatworms to Different Oxygen Tensions.

Antioxidants (Basel, Switzerland), 11(6): pii:antiox11061102.

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.

RevDate: 2022-07-06

P K, Chakraborty B, Rani V, et al (2022)

Rationally designed far-red emitting styryl chromones and a magnetic nanoconjugate for strip-based 'on-site' detection of metabolic markers.

Journal of materials chemistry. B, 10(26):5071-5085.

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.

RevDate: 2022-06-17

Della Rocca G, Papini A, Posarelli I, et al (2022)

Ultrastructure of Terpene and Polyphenol Synthesis in the Bark of Cupressus sempervirens After Seiridium cardinale Infection.

Frontiers in microbiology, 13:886331.

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).

RevDate: 2022-06-17
CmpDate: 2022-06-17

Wu B, Hao W, MP Cox (2022)

Reconstruction of gene innovation associated with major evolutionary transitions in the kingdom Fungi.

BMC biology, 20(1):144.

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.

RevDate: 2022-06-14

Brischigliaro M, Cabrera-Orefice A, Sturlese M, et al (2022)

CG7630 is the Drosophila melanogaster homolog of the cytochrome c oxidase subunit COX7B.

EMBO reports [Epub ahead of print].

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.

RevDate: 2022-06-15
CmpDate: 2022-06-15

Paredes GF, Viehboeck T, Markert S, et al (2022)

Differential regulation of degradation and immune pathways underlies adaptation of the ectosymbiotic nematode Laxus oneistus to oxic-anoxic interfaces.

Scientific reports, 12(1):9725.

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.

RevDate: 2022-07-05
CmpDate: 2022-06-30

Jiang X, Coroian D, Barahona E, et al (2022)

Functional Nitrogenase Cofactor Maturase NifB in Mitochondria and Chloroplasts of Nicotiana benthamiana.

mBio, 13(3):e0026822.

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.

RevDate: 2022-06-14
CmpDate: 2022-06-14

Groux K, Verschueren A, Nanteau C, et al (2022)

Dynamic full-field optical coherence tomography allows live imaging of retinal pigment epithelium stress model.

Communications biology, 5(1):575.

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.

RevDate: 2022-06-10

Ruiz D, Santibañez M, Lavín BA, et al (2022)

Evolution of Mitochondrially Derived Peptides Humanin and MOTSc, and Changes in Insulin Sensitivity during Early Gestation in Women with and without Gestational Diabetes.

Journal of clinical medicine, 11(11): pii:jcm11113003.

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.

RevDate: 2022-06-13
CmpDate: 2022-06-13

Cartalas J, Coudray L, A Gobert (2022)

How RNases Shape Mitochondrial Transcriptomes.

International journal of molecular sciences, 23(11): pii:ijms23116141.

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.

RevDate: 2022-06-13
CmpDate: 2022-06-13

Eugenin E, Camporesi E, C Peracchia (2022)

Direct Cell-Cell Communication via Membrane Pores, Gap Junction Channels, and Tunneling Nanotubes: Medical Relevance of Mitochondrial Exchange.

International journal of molecular sciences, 23(11): pii:ijms23116133.

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.

RevDate: 2022-06-28

Tassé M, Choquette T, Angers A, et al (2022)

The longest mitochondrial protein in metazoans is encoded by the male-transmitted mitogenome of the bivalve Scrobicularia plana.

Biology letters, 18(6):20220122.

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.

RevDate: 2022-06-16
CmpDate: 2022-06-16

Choudhury S, Ananthanarayanan V, KG Ayappa (2022)

Coupling of mitochondrial population evolution to microtubule dynamics in fission yeast cells: a kinetic Monte Carlo study.

Soft matter, 18(23):4483-4492.

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.

RevDate: 2022-06-06

Simon M, Durand S, Ricou A, et al (2022)

APOK3, a pollen killer antidote in Arabidopsis thaliana.

Genetics pii:6603116 [Epub ahead of print].

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 twelve 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.

RevDate: 2022-06-30

Dawson NJ, GR Scott (2022)

Adaptive increases in respiratory capacity and O2 affinity of subsarcolemmal mitochondria from skeletal muscle of high-altitude deer mice.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36(7):e22391.

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.

RevDate: 2022-07-02

Hautekiet P, Saenen ND, Aerts R, et al (2022)

Higher buccal mtDNA content is associated with residential surrounding green in a panel study of primary school children.

Environmental research, 213:113551 pii:S0013-9351(22)00878-7 [Epub ahead of print].

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.

RevDate: 2022-06-13
CmpDate: 2022-06-13

Bremer N, Tria FDK, Skejo J, et al (2022)

Ancestral State Reconstructions Trace Mitochondria But Not Phagocytosis to the Last Eukaryotic Common Ancestor.

Genome biology and evolution, 14(6):.

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.

RevDate: 2022-06-06
CmpDate: 2022-06-02

Calatrava V, Stephens TG, Gabr A, et al (2022)

Retrotransposition facilitated the establishment of a primary plastid in the thecate amoeba Paulinella.

Proceedings of the National Academy of Sciences of the United States of America, 119(23):e2121241119.

SignificancePrimary endosymbiosis allowed the evolution of complex life on Earth. In this process, a prokaryote was engulfed and retained in the cytoplasm of another microbe, where it developed into a new organelle (mitochondria and plastids). During organelle evolution, genes from the endosymbiont are transferred to the host nuclear genome, where they must become active despite differences in the genetic nature of the "partner" organisms. Here, we show that in the amoeba Paulinella micropora, which harbors a nascent photosynthetic organelle, the "copy-paste" mechanism of retrotransposition allowed domestication of endosymbiont-derived genes in the host nuclear genome. This duplication mechanism is widespread in eukaryotes and may be a major facilitator for host-endosymbiont integration and the evolution of organelles.

RevDate: 2022-06-02
CmpDate: 2022-06-02

Li M, Chen WT, Zhang QL, et al (2022)

Mitochondrial phylogenomics provides insights into the phylogeny and evolution of spiders (Arthropoda: Araneae).

Zoological research, 43(4):566-584.

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.

RevDate: 2022-06-02
CmpDate: 2022-06-02

Kodama Y, M Fujishima (2022)

Endosymbiotic Chlorella variabilis reduces mitochondrial number in the ciliate Paramecium bursaria.

Scientific reports, 12(1):8216.

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.

RevDate: 2022-06-22
CmpDate: 2022-06-21

Jiang YJ, Jin J, Nan QY, et al (2022)

Coenzyme Q10 attenuates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in unilateral ureteral obstruction.

International immunopharmacology, 108:108868.

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.

RevDate: 2022-06-08
CmpDate: 2022-06-02

Zhang L, Liu K, Zhuan Q, et al (2022)

Mitochondrial Calcium Disorder Affects Early Embryonic Development in Mice through Regulating the ERK/MAPK Pathway.

Oxidative medicine and cellular longevity, 2022:8221361.

The homeostasis of mitochondrial calcium ([Ca2+]mt) in oocytes plays a critical role in maintaining normal reproductive cellular progress such as meiosis. However, little is known about the association between [Ca2+]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 [Ca2+]mt concentrations. The imbalance of [Ca2+]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 [Ca2+]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 [Ca2+]mt homeostasis in early embryonic development and also demonstrate a new mechanism of MAPK signaling regulated by [Ca2+]mt that influences epigenetic modification.

RevDate: 2022-05-31
CmpDate: 2022-05-31

Xie DM, Zhang Q, Xin LK, et al (2022)

Cloning and Functional Characterization of Two Germacrene A Oxidases Isolated from Xanthium sibiricum.

Molecules (Basel, Switzerland), 27(10): pii:molecules27103322.

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.

RevDate: 2022-05-31
CmpDate: 2022-05-31

Popadin K, Gunbin K, Peshkin L, et al (2022)

Mitochondrial Pseudogenes Suggest Repeated Inter-Species Hybridization among Direct Human Ancestors.

Genes, 13(5): pii:genes13050810.

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).

RevDate: 2022-06-19

Xu JJ, Hu M, Yang L, et al (2022)

How plants synthesize coenzyme Q.

Plant communications pii:S2590-3462(22)00096-7 [Epub ahead of print].

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.

RevDate: 2022-05-27
CmpDate: 2022-05-26

Schärer L (2022)

Evolution: Mitochondrial lodgers can take over in hermaphroditic snails.

Current biology : CB, 32(10):R477-R479.

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.

RevDate: 2022-06-24

Yu G, Nakajima K, Gruber A, et al (2022)

Mitochondrial phosphoenolpyruvate carboxylase contributes to carbon fixation in the diatom Phaeodactylum tricornutum at low inorganic carbon concentrations.

The New phytologist [Epub ahead of print].

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.

RevDate: 2022-05-31
CmpDate: 2022-05-23

Huynen MA, DM Elurbe (2022)

Mitochondrial complex complexification.

Science (New York, N.Y.), 376(6595):794-795.

Variation in complex composition provides clues about the function of individual subunits.

RevDate: 2022-06-14

Vujovic F, Hunter N, RM Farahani (2022)

Notch ankyrin domain: evolutionary rise of a thermodynamic sensor.

Cell communication and signaling : CCS, 20(1):66.

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 Notchon to Notchoff state, characterised by dissociation of Notch intracellular domain (NICD) from DNA-bound RBPJ. Here we provide evidence that transitioning to the Notchoff 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 Notchoff 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 Notchon state via the ankyrin domain and is eventually switched off in a temperature-dependent manner. Video abstract.

RevDate: 2022-06-14
CmpDate: 2022-06-14

da Silva E Silva LH, da Silva FS, Medeiros DBA, et al (2022)

Description of the mitogenome and phylogeny of Aedes spp. (Diptera: Culicidae) from the Amazon region.

Acta tropica, 232:106500.

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.

RevDate: 2022-05-26

Maldonado JA, Firneno TJ, Hall AS, et al (2022)

Parthenogenesis doubles the rate of amino acid substitution in whiptail mitochondria.

Evolution; international journal of organic evolution [Epub ahead of print].

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.

RevDate: 2022-06-03
CmpDate: 2022-06-03

Sandamalika WMG, Udayantha HMV, Liyanage DS, et al (2022)

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.

Fish & shellfish immunology, 125:266-275.

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.

RevDate: 2022-06-21

Bates M, Keller-Findeisen J, Przybylski A, et al (2022)

Optimal precision and accuracy in 4Pi-STORM using dynamic spline PSF models.

Nature methods, 19(5):603-612.

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.

RevDate: 2022-06-14
CmpDate: 2022-06-14

Xu X, Yu L, Li F, et al (2022)

Phylogenetic placement and species delimitation of the crab spider genus Phrynarachne (Araneae: Thomisidae) from China.

Molecular phylogenetics and evolution, 173:107521.

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.

RevDate: 2022-05-19
CmpDate: 2022-05-19

Lee J, CS Willett (2022)

Frequent Paternal Mitochondrial Inheritance and Rapid Haplotype Frequency Shifts in Copepod Hybrids.

The Journal of heredity, 113(2):171-183.

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.

RevDate: 2022-05-18
CmpDate: 2022-05-17

Bonturi CR, Silva Teixeira AB, Rocha VM, et al (2022)

Plant Kunitz Inhibitors and Their Interaction with Proteases: Current and Potential Pharmacological Targets.

International journal of molecular sciences, 23(9):.

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.

RevDate: 2022-05-16

Benz R (2021)

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.

Frontiers in physiology, 12:734226.

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.

RevDate: 2022-05-16
CmpDate: 2022-05-16

Corsaro D (2022)

Insights into Microsporidia Evolution from Early Diverging Microsporidia.

Experientia supplementum (2012), 114:71-90.

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.

RevDate: 2022-06-15

Kidd KK, Evsanaa B, Togtokh A, et al (2022)

North Asian population relationships in a global context.

Scientific reports, 12(1):7214.

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.

RevDate: 2022-07-05

Zhou W, Zhao Z, Yu Z, et al (2022)

Mitochondrial transplantation therapy inhibits the proliferation of malignant hepatocellular carcinoma and its mechanism.

Mitochondrion, 65:11-22 pii:S1567-7249(22)00038-1 [Epub ahead of print].

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.

RevDate: 2022-06-27

Niu Y, Lu Y, Song W, et al (2022)

Assembly and comparative analysis of the complete mitochondrial genome of three Macadamia species (M. integrifolia, M. ternifolia and M. tetraphylla).

PloS one, 17(5):e0263545.

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.

RevDate: 2022-05-31
CmpDate: 2022-05-04

Liu H, Zhao W, Hua W, et al (2022)

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.

BMC genomics, 23(1):339.

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.

RevDate: 2022-06-01

Das R, Kumar A, Dalai R, et al (2022)

Cytochrome C interacts with the pathogenic mutational hotspot region of TRPV4 and forms complexes that differ in mutation and metal ion-sensitive manner.

Biochemical and biophysical research communications, 611:172-178.

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 Ca2+-sensitive manner. This interaction is also variable and sensitive to other divalent and trivalent cations (i.e., Cu2+, Mn2+, Ni2+, Zn2+, Fe3+). 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.

RevDate: 2022-05-26
CmpDate: 2022-05-26

David P, Degletagne C, Saclier N, et al (2022)

Extreme mitochondrial DNA divergence underlies genetic conflict over sex determination.

Current biology : CB, 32(10):2325-2333.e6.

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 times4 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.

RevDate: 2022-04-30

De Pinto V, Mahalakshmi R, A Messina (2022)

Editorial: VDAC Structure and Function: An Up-to-Date View.

Frontiers in physiology, 13:871586.

RevDate: 2022-04-29

Yi L, Liu B, Nixon PJ, et al (2022)

Recent Advances in Understanding the Structural and Functional Evolution of FtsH Proteases.

Frontiers in plant science, 13:837528.

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.

RevDate: 2022-05-17
CmpDate: 2022-05-17

Kodagoda YK, Liyanage DS, Omeka WKM, et al (2022)

Molecular characterization, expression, and functional analysis of cystatin B in the big-belly seahorse (Hippocampus abdominalis).

Fish & shellfish immunology, 124:442-453.

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.

RevDate: 2022-05-31
CmpDate: 2022-04-26

Juskeviciene R, Fritz AK, Brilkova M, et al (2022)

Phenotype of Mrps5-Associated Phylogenetic Polymorphisms Is Intimately Linked to Mitoribosomal Misreading.

International journal of molecular sciences, 23(8):.

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 MrpS5G315R/G315R mice did not show a phenotype distinct from wild-type animals.

RevDate: 2022-04-29

Russo C, Valle MS, Casabona A, et al (2022)

Vitamin D Impacts on Skeletal Muscle Dysfunction in Patients with COPD Promoting Mitochondrial Health.

Biomedicines, 10(4):.

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.

RevDate: 2022-04-29

Hambardikar V, Guitart-Mampel M, Scoma ER, et al (2022)

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.

Antioxidants (Basel, Switzerland), 11(4):.

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 13C-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.

RevDate: 2022-05-09
CmpDate: 2022-05-09

Coleman PS, RA Parlo (2022)

Cancer's camouflage: Microvesicle shedding from cholesterol-rich tumor plasma membranes might blindfold first-responder immunosurveillance strategies.

European journal of cell biology, 101(2):151219.

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.

RevDate: 2022-05-24
CmpDate: 2022-05-24

Chen Q, Chen L, Liao CQ, et al (2022)

Comparative mitochondrial genome analysis and phylogenetic relationship among lepidopteran species.

Gene, 830:146516.

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))))))))))))).

RevDate: 2022-06-06
CmpDate: 2022-06-06

Gil Del Alcazar CR, Trinh A, Alečković M, et al (2022)

Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer.

Cancer immunology research, 10(6):680-697.

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.

RevDate: 2022-05-27

Fields PD, Waneka G, Naish M, et al (2022)

Complete Sequence of a 641-kb Insertion of Mitochondrial DNA in the Arabidopsis thaliana Nuclear Genome.

Genome biology and evolution, 14(5):.

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.

RevDate: 2022-04-23

Mendez-Romero O, Ricardez-García C, Castañeda-Tamez P, et al (2022)

Thriving in Oxygen While Preventing ROS Overproduction: No Two Systems Are Created Equal.

Frontiers in physiology, 13:874321.

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.

RevDate: 2022-04-20

Egusquiza-Alvarez CA, M Robles-Flores (2022)

An approach to p32/gC1qR/HABP1: a multifunctional protein with an essential role in cancer.

Journal of cancer research and clinical oncology [Epub ahead of print].

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.

RevDate: 2022-07-01
CmpDate: 2022-07-01

Nakabachi A, NA Moran (2022)

Extreme Polyploidy of Carsonella, an Organelle-Like Bacterium with a Drastically Reduced Genome.

Microbiology spectrum, 10(3):e0035022.

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 × 104 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.

RevDate: 2022-05-10

Yuan F, X Lan (2022)

Sequencing the organelle genomes of Bougainvillea spectabilis and Mirabilis jalapa (Nyctaginaceae).

BMC genomic data, 23(1):28.

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.

RevDate: 2022-04-19
CmpDate: 2022-04-13

Tsai HC, Hsieh CH, Hsu CW, et al (2022)

Cloning and Organelle Expression of Bamboo Mitochondrial Complex I Subunits Nad1, Nad2, Nad4, and Nad5 in the Yeast Saccharomyces cerevisiae.

International journal of molecular sciences, 23(7):.

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+.

RevDate: 2022-04-19
CmpDate: 2022-04-13

Kasperski A (2022)

Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue.

International journal of molecular sciences, 23(7):.

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.

RevDate: 2022-04-15
CmpDate: 2022-04-13

Scaltsoyiannes V, Corre N, Waltz F, et al (2022)

Types and Functions of Mitoribosome-Specific Ribosomal Proteins across Eukaryotes.

International journal of molecular sciences, 23(7):.

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.

RevDate: 2022-04-23
CmpDate: 2022-04-13

Snell TW, J Carberry (2022)

Astaxanthin Bioactivity Is Determined by Stereoisomer Composition and Extraction Method.

Nutrients, 14(7):.

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.

RevDate: 2022-04-10

Zhu D, Li X, Y Tian (2022)

Mitochondrial-to-nuclear communication in aging: an epigenetic perspective.

Trends in biochemical sciences pii:S0968-0004(22)00067-6 [Epub ahead of print].

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.

RevDate: 2022-04-11
CmpDate: 2022-04-11

Chen Z, Liu F, Li D, et al (2022)

Four new species of the primitively segmented spider genus Songthela (Mesothelae, Liphistiidae) from Chongqing Municipality, China.

Zootaxa, 5091(4):546-558.

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.

RevDate: 2022-04-11
CmpDate: 2022-04-11

Lobon-Rovira J, Conradie W, Pinto PV, et al (2022)

Systematic revision of Afrogecko ansorgii (Boulenger, 1907) (Sauria: Gekkonidae) from western Angola.

Zootaxa, 5124(4):401-430.

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.

RevDate: 2022-04-11
CmpDate: 2022-04-11

Takano KT, Gao JJ, Hu YG, et al (2021)

Phylogeny, taxonomy and flower-breeding ecology of the Colocasiomyia cristata species group (Diptera: Drosophilidae), with descriptions of ten new species.

Zootaxa, 5079(1):170.

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.

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In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

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In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

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