Mitochondrion最新文献

{"title":"The maternal genetic history of tribal populations of Chhattisgarh, India","authors":"Shivani Dixit ,&nbsp;Pankaj Shrivastava ,&nbsp;Jaison Jeevan Sequeira ,&nbsp;Mohammed S Mustak ,&nbsp;Manisha Rana ,&nbsp;Pushpesh Kushwaha ,&nbsp;Divya Shrivastava ,&nbsp;R.K. Kumawat ,&nbsp;Prajjval Pratap Singh ,&nbsp;Sachin K. Tiwary ,&nbsp;Neeraj K. Chauhan ,&nbsp;Gyaneshwer Chaubey","doi":"10.1016/j.mito.2024.101970","DOIUrl":"10.1016/j.mito.2024.101970","url":null,"abstract":"<div><div>The central region of India boasts a rich tribal heritage and the highest number of tribal populations in the country. Analysing the genetic history of this population can offer valuable insights into various demographic processes that shaped the gene pool of present-day settlers of this region. In this study, we utilize a recently validated Next-generation sequencing (NGS) technique to sequence 24 tribal mitogenomes from the Chhattisgarh population for genetic ancestry and forensic analysis. The identified ancient haplogroups in this population can be traced back to the pre-Last Glacial Maximum (LGM) period. Our Bayesian analysis provides evidence for maternal ancestral expansion following the earliest Out-of-Africa migration, followed by a prolonged steady phase. We identified three basal founding haplogroups, M2, R5, and U2 in the Chhattisgarh region that diversified during the Neolithic period. Indistinct distribution pattern of these haplogroups among tribes and castes suggests that the maternal ancestry of Chhattisgarh population predates any kind of social stratification that exists today in the Indian subcontinent. Furthermore, our analysis suggests that this region remained unaffected by the Last Glacial Maximum. The forensic analysis of the mitogenomes demonstrates a high power of discrimination (0.9256) within the Chhattisgarh population, thus supporting the applicability of mitogenome NGS technology in forensic contexts.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"79 ","pages":"Article 101970"},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial genome-derived circRNAs: Orphan epigenetic regulators in molecular biology","authors":"Nima Sanadgol ,&nbsp;Javad Amini ,&nbsp;Roghayeh Khalseh ,&nbsp;Mostafa Bakhshi ,&nbsp;Arezoo Nikbin ,&nbsp;Cordian Beyer ,&nbsp;Adib Zendehdel","doi":"10.1016/j.mito.2024.101968","DOIUrl":"10.1016/j.mito.2024.101968","url":null,"abstract":"<div><div>Mitochondria are vital for cellular activities, influencing ATP production, Ca2⁺ signaling, and reactive oxygen species generation. It has been proposed that nuclear genome-derived circular RNAs (circRNAs) play a role in biological processes. For the first time, this study aims to comprehensively explore experimentally confirmed human mitochondrial genome-derived circRNAs (mt-circRNAs) via in-silico analysis. We utilized wide-ranging bioinformatics tools to anticipate their roles in molecular biology, involving miRNA sponging, protein antagonism, and peptide translation. Among five well-characterized mt-circRNAs, SCAR/mc-COX2 stands out as particularly significant with the potential to sponge around 41 different miRNAs, which target several genes mostly involved in endocytosis, MAP kinase, and PI3K-Akt pathways. Interestingly, circMNTND5 and mecciND1 specifically interact with miRNAs through their unique back-splice junction sequence. These exclusively targeted miRNAs (has-miR-5186, 6888-5p, 8081, 924, 672-5p) are predominantly associated with insulin secretion, proteoglycans in cancer, and MAPK signaling pathways. Moreover, all mt-circRNAs intricately affect the P53 pathway through miRNA sequestration. Remarkably, mc-COX2 and circMNTND5 appear to be involved in the RNA’s biogenesis by antagonizing AGO1/2, EIF4A3, and DGCR8. All mt-circRNAs engaged with IGF2BP proteins crucial in redox signaling, and except mecciND1, they all potentially generate at least one protein resembling the immunoglobulin heavy chain protein. Given P53′s function as a redox-sensitive transcription factor, and insulin’s role as a crucial regulator of energy metabolism, their indirect interplay with mt-circRNAs could influence cellular outcomes. However, due to limited attention and infrequent data availability, it is advisable to conduct more thorough investigations to gain a deeper understanding of the functions of mt-circRNA.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"79 ","pages":"Article 101968"},"PeriodicalIF":3.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newer mitochondrial dynamics and their role of calcium signalling in liver regeneration","authors":"Onkar Bedi ,&nbsp;Vaibhav Sapra ,&nbsp;Manish Kumar ,&nbsp;Pawan Krishan","doi":"10.1016/j.mito.2024.101969","DOIUrl":"10.1016/j.mito.2024.101969","url":null,"abstract":"<div><p>Liver regeneration is a crucial process involved in cellular proliferation, differentiation, and tissue repair. Calcium signaling impact key pathways<!--> <!--> like hepatocyte growth factor-Met-tyrosine kinase (HGF-Met) transduction pathway, the epidermal growth factor receptor (EGFR) signaling and Ca-mediated nuclear SKHep1 cell proliferation pathway. Intracellular hepatocyte calcium stores are considered as base for the induction of ca-mediated regeneration process. Calcium signaling interplays with HGF, TGF-β, and NF-κB signaling, influence stem cell behavior and triggers MAPK cascade. The mitochondria calcium is impacting on liver rejuvenation by regulating apoptosis and cell division.<!--> <!--> In conclusion, it is stated that calcium-signaling holds promise for therapeutic liver interventions.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"79 ","pages":"Article 101969"},"PeriodicalIF":3.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Krebs cycle derivatives, dimethyl fumarate and itaconate, control metabolic reprogramming in inflammatory human microglia cell line","authors":"Moris Sangineto ,&nbsp;Martina Ciarnelli ,&nbsp;Archana Moola ,&nbsp;Vidyasagar Naik Bukke ,&nbsp;Tommaso Cassano ,&nbsp;Rosanna Villani ,&nbsp;Antonino D. Romano ,&nbsp;Giuseppe Di Gioia ,&nbsp;Carlo Avolio ,&nbsp;Gaetano Serviddio","doi":"10.1016/j.mito.2024.101966","DOIUrl":"10.1016/j.mito.2024.101966","url":null,"abstract":"<div><p>Metabolic reprogramming drives inflammatory activity in macrophages, including microglia, with Krebs cycle (KC) intermediates playing a crucial role as signaling molecules. Here, we show that the bioenergetic profile of LPS-activated human microglial<!--> <!-->clone 3 cell line (HMC3) is characterized by high levels of glycolysis and mitochondrial (mt) respiration, and the treatment with KC derivatives, namely dimethyl-fumarate (DMF) and itaconate (ITA), almost restores normal metabolism. However, despite comparable bioenergetic and anti-inflammatory effects, the mt hyper-activity was differentially modulated by DMF and ITA. DMF normalized complex I activity, while ITA dampened both complex I and II hyper-activity counteracting oxidative stress more efficiently.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"79 ","pages":"Article 101966"},"PeriodicalIF":3.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924001247/pdfft?md5=6a5becc343b5697d574ecae4cead3197&pid=1-s2.0-S1567724924001247-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The multifaceted effects of mitochondria in kidney diseases","authors":"Jia-Le Xue ,&nbsp;Jia-Ling Ji ,&nbsp;Yan Zhou ,&nbsp;Yao Zhang ,&nbsp;Bi-Cheng Liu ,&nbsp;Rui-Xia Ma ,&nbsp;Zuo-Lin Li","doi":"10.1016/j.mito.2024.101957","DOIUrl":"10.1016/j.mito.2024.101957","url":null,"abstract":"<div><p>Mitochondria serve as the primary site for aerobic respiration within cells, playing a crucial role in maintaining cellular homeostasis. To maintain homeostasis and meet the diverse demands of the cells, mitochondria have evolved intricate systems of quality control, mainly including mitochondrial dynamics, mitochondrial autophagy (mitophagy) and mitochondrial biogenesis. The kidney, characterized by its high energy requirements, is particularly abundant in mitochondria. Interestingly, the mitochondria display complex behaviors and functions. When the kidney is suffered from obstructive, ischemic, hypoxic, oxidative, or metabolic insults, the dysfunctional mitochondrial derived from the defects in the mitochondrial quality control system contribute to cellular inflammation, cellular senescence, and cell death, posing a threat to the kidney. However, in addition to causing injury to the kidney in several cases, mitochondria also exhibit protective effect on the kidney. In recent years, accumulating evidence indicated that mitochondria play a crucial role in adaptive repair following kidney diseases caused by various etiologies. In this article, we comprehensively reviewed the current understanding about the multifaceted effects of mitochondria on kidney diseases and their therapeutic potential.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"79 ","pages":"Article 101957"},"PeriodicalIF":3.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association analysis of mitochondrial DNA heteroplasmic variants: Methods and application","authors":"Xianbang Sun ,&nbsp;Katia Bulekova ,&nbsp;Jian Yang ,&nbsp;Meng Lai ,&nbsp;Achilleas N. Pitsillides ,&nbsp;Xue Liu ,&nbsp;Yuankai Zhang ,&nbsp;Xiuqing Guo ,&nbsp;Qian Yong ,&nbsp;Laura M. Raffield ,&nbsp;Jerome I. Rotter ,&nbsp;Stephen S. Rich ,&nbsp;Goncalo Abecasis ,&nbsp;April P. Carson ,&nbsp;Ramachandran S. Vasan ,&nbsp;Joshua C. Bis ,&nbsp;Bruce M. Psaty ,&nbsp;Eric Boerwinkle ,&nbsp;Annette L. Fitzpatrick ,&nbsp;Claudia L. Satizabal ,&nbsp;Chunyu Liu","doi":"10.1016/j.mito.2024.101954","DOIUrl":"10.1016/j.mito.2024.101954","url":null,"abstract":"<div><p>We rigorously assessed a comprehensive association testing framework for heteroplasmy, employing both simulated and real-world data. This framework employed a variant allele fraction (VAF) threshold and harnessed multiple gene-based tests for robust identification and association testing of heteroplasmy. Our simulation studies demonstrated that gene-based tests maintained an appropriate type I error rate at α = 0.001. Notably, when 5 % or more heteroplasmic variants within a target region were linked to an outcome, burden-extension tests (including the adaptive burden test, variable threshold burden test, and z-score weighting burden test) outperformed the sequence kernel association test (SKAT) and the original burden test. Applying this framework, we conducted association analyses on whole-blood derived heteroplasmy in 17,507 individuals of African and European ancestries (31 % of African Ancestry, mean age of 62, with 58 % women) with whole genome sequencing data. We performed both cohort- and ancestry-specific association analyses, followed by meta-analysis on both pooled samples and within each ancestry group. Our results suggest that mtDNA-encoded genes/regions are likely to exhibit varying rates in somatic aging, with the notably strong associations observed between heteroplasmy in the <em>RNR1</em> and <em>RNR2</em> genes (<em>p</em> &lt; 0.001) and advance aging by the Original Burden test. In contrast, SKAT identified significant associations (<em>p</em> &lt; 0.001) between diabetes and the aggregated effects of heteroplasmy in several protein-coding genes. Further research is warranted to validate these findings. In summary, our proposed statistical framework represents a valuable tool for facilitating association testing of heteroplasmy with disease traits in large human populations.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"79 ","pages":"Article 101954"},"PeriodicalIF":3.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial acyl carrier protein, Acp1, required for iron-sulfur cluster assembly in mitochondria and cytoplasm in Saccharomyces cerevisiae","authors":"Ashutosh K. Pandey ,&nbsp;Heeyong Yoon ,&nbsp;Jayashree Pain ,&nbsp;Andrew Dancis ,&nbsp;Debkumar Pain","doi":"10.1016/j.mito.2024.101955","DOIUrl":"10.1016/j.mito.2024.101955","url":null,"abstract":"<div><p>Mitochondria perform vital biosynthetic processes, including fatty acid synthesis and iron-sulfur (FeS) cluster biogenesis. In <em>Saccharomyces cerevisiae</em> mitochondria, the acyl carrier protein Acp1 participates in type II fatty acid synthesis, requiring a 4-phosphopantetheine (PP) prosthetic group. Acp1 also interacts with the mitochondrial FeS cluster assembly complex that contains the cysteine desulfurase Nfs1. Here we investigated the role of Acp1 in FeS cluster biogenesis in mitochondria and cytoplasm. In the Acp1-depleted (Acp1↓) cells, biogenesis of mitochondrial FeS proteins was impaired, likely due to greatly reduced Nfs1 protein and/or its persulfide-forming activity. Formation of cytoplasmic FeS proteins was also deficient, suggesting a disruption in generating the (Fe-S)_int intermediate, that is exported from mitochondria and is subsequently utilized for cytoplasmic FeS cluster assembly. Iron homeostasis was perturbed, with enhanced iron uptake into the cells and accumulation of iron in mitochondria. The Δppt2 strain, lacking the mitochondrial ability to add PP to Acp1, phenocopied the Acp1↓ cells. These data suggest that the holo form of Acp1 with the PP-conjugated acyl chain is required for stability of the Nfs1 protein and/or stimulation of its persulfide-forming activity. Thus, mitochondria lacking Acp1 (or Ppt2) cannot support FeS cluster biogenesis in mitochondria or cytoplasm, leading to disrupted iron homeostasis.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"79 ","pages":"Article 101955"},"PeriodicalIF":3.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924001132/pdfft?md5=32453584b8407f990380d5cd00b703ec&pid=1-s2.0-S1567724924001132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the anti-apoptotic role of Plasmodium falciparum Prohibitin-2 (PfPhb2) in maintaining mitochondrial homeostasis","authors":"Shilpi Jain,&nbsp;Monika Narwal,&nbsp;Md Omair Anwar,&nbsp;Neha Prakash,&nbsp;Asif Mohmmed","doi":"10.1016/j.mito.2024.101956","DOIUrl":"10.1016/j.mito.2024.101956","url":null,"abstract":"<div><p>The functional mitochondrion is vital for the propagation of the malaria parasite in the human host. Members of the SPFH protein family, Prohibitins (PHBs), are known to play crucial roles in maintaining mitochondrial homeostasis and cellular functions. Here, we have functionally characterized the homologue of the <em>Plasmodium falciparum</em> <!-->Prohibitin-2 (<em>Pf</em>Phb2) protein. A transgenic parasite line, generated using the selection-linked integration (SLI) strategy for C-terminal tagging, was utilized for cellular localization as well as for inducible knock-down of <em>Pf</em>Phb2. We show that <em>Pf</em>Phb2 localizes in the parasite mitochondrion during the asexual life cycle. Inducible knock-down of <em>Pf</em>Phb2 by <em>Glm</em>S ribozyme caused no significant effect on the growth and multiplication of parasites. However, depletion of <em>Pf</em>Phb2 under mitochondrial-specific stress conditions, induced by inhibiting the essential mitochondrial AAA-protease, ClpQ protease, results in enhanced inhibition of parasite growth, mitochondrial ROS production, mitochondrial membrane potential loss and led to mitochondrial fission/fragmentation, ultimately culminating in apoptosis-like cell-death. Further, <em>Pf</em>Phb2 depletion renders the parasites more susceptible to mitochondrial targeting drug proguanil. These data suggest the functional involvement of <em>Pf</em>Phb2 along with ClpQ protease in stabilization of various mitochondrial proteins to maintain mitochondrial homeostasis and functioning. Overall, we show that <em>Pf</em>Phb2 has an anti-apoptotic role in maintaining mitochondrial homeostasis in the parasite.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"79 ","pages":"Article 101956"},"PeriodicalIF":3.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SDHAF2 facilitates mitochondrial respiration through stabilizing succinate dehydrogenase and cytochrome c oxidase assemblies","authors":"Chang-Lin Chen ,&nbsp;Takaya Ishihara ,&nbsp;Soumyadip Pal ,&nbsp;Wei-Ling Huang ,&nbsp;Emi Ogasawara ,&nbsp;Chuang-Rung Chang ,&nbsp;Naotada Ishihara","doi":"10.1016/j.mito.2024.101952","DOIUrl":"10.1016/j.mito.2024.101952","url":null,"abstract":"<div><p>Succinate dehydrogenase (SDH) plays pivotal roles in maintaining cellular metabolism, modulating regulatory control over both the tricarboxylic acid cycle and oxidative phosphorylation to facilitate energy production within mitochondria. Given that SDH malfunction may serve as a hallmark triggering pseudo-hypoxia signaling and promoting tumorigenesis, elucidating the impact of SDH assembly defects on mitochondrial functions and cellular responses is of paramount importance. In this study, we aim to clarify the role of SDHAF2, one assembly factor of SDH, in mitochondrial respiratory activities. To achieve this, we utilize the CRISPR/Cas9 system to generate SDHAF2 knockout in HeLa cells and examine mitochondrial respiratory functions. Our findings demonstrate a substantial reduction in oxygen consumption rate in SDHAF2 knockout cells, akin to cells with inhibited SDH activity. In addition, in our in-gel activity assays reveal a significant decrease not only in SDH activity but also in cytochrome <em>c</em> oxidase (COX) activity in SDHAF2 knockout cells. The reduced COX activity is attributed to the assembly defect and remains independent of SDH inactivation or SDH complex disassembly. Together, our results indicate a critical role of SDHAF2 in regulating respiration by facilitating the assembly of COX.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"79 ","pages":"Article 101952"},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924001107/pdfft?md5=20a0aab34c62f86080250ebefe848de4&pid=1-s2.0-S1567724924001107-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of mitochondrial genomic variation with successful neurological aging","authors":"Nicole Tamvaka ,&nbsp;Michael G. Heckman ,&nbsp;Patrick W. Johnson ,&nbsp;Alexandra I. Soto-Beasley ,&nbsp;Ronald L. Walton ,&nbsp;Shunsuke Koga ,&nbsp;Ryan J. Uitti ,&nbsp;Francine Parfitt ,&nbsp;Michelle R. Graff-Radford ,&nbsp;Zbigniew K. Wszolek ,&nbsp;Neill Graff-Radford ,&nbsp;Rebecca R. Valentino ,&nbsp;Owen A. Ross","doi":"10.1016/j.mito.2024.101948","DOIUrl":"10.1016/j.mito.2024.101948","url":null,"abstract":"<div><p>Mitochondrial health is an integral factor in aging, with mitochondrial dysfunction known to increase with age and contribute to the development of age-related neurodegenerative disorders. Additionally, the mitochondrial genome (mtDNA) has been shown to acquire potentially damaging somatic variation as part of the aging process, while mtDNA single nucleotide polymorphism (SNPs) have been shown to be both protective and detrimental for various neurodegenerative diseases. Yet, little is known about the involvement of mtDNA variation in longevity and successful neurological aging. In this study, we examined the association of mtDNA SNPs, in the form of mitochondrial haplogroups, with successful neurological aging in 1,405 unrelated neurologically healthy subjects. Although not quite significant after correcting for multiple testing (P &lt; 0.0017 considered as significant), we detected a nominally significant association between the I haplogroup (N = 45, 3.2 %) and a younger age (β: −5.00, P = 0.006), indicating that this haplogroup is observed less frequently in older neurologically healthy individuals and may be associated with decreased survival. Replication of this finding in independent neurologically healthy cohorts will be imperative for shaping our understanding of the biological processes underlying healthy neurological aging.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101948"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}