Mitochondrion最新文献

{"title":"Mitochondrial quality control in exercise-mitigated muscular atrophy.","authors":"Jingcheng Fan, Xin Wen, Xuemei Duan, Xinyi Zhu, Jianzheng Bai, Tan Zhang","doi":"10.1016/j.mito.2025.102074","DOIUrl":"10.1016/j.mito.2025.102074","url":null,"abstract":"<p><p>Muscle atrophy is a loss of muscle mass, posing a huge burden on patients and society. Increased protein degradation, decreased protein synthesis, inflammatory response, oxidative stress, and mitochondrial dysfunction are risk factors of muscular atrophy. Mitochondrial quality control (MQC) processes maintain mitochondrial health, which is essential to maintain skeletal muscle structural and functional integrity. Of note, it is widely acknowledged that regular exercise induces significant improvements in muscular atrophy. Mechanistically, exercise reinforces mitochondrial function through MQC, as well as mitigate muscular atrophy. However, the role and molecular mechanism of MQC in exercise-attenuated muscular atrophy have not yet fully elucidated. Here, we review the current knowledge relevant to MQC in the context of muscular atrophy, and focus on MQC in exercise-mediated anti-atrophic effect, which may be conductive to muscular atrophy prevention and therapy through targeting mitochondria.</p>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":" ","pages":"102074"},"PeriodicalIF":4.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753789","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 Transcription: A click-chemistry derived detection methodology forgoing the use of radiation in in vitro analyses.","authors":"Anthony Stapon, Miguel Garcia-Diaz","doi":"10.1016/j.mito.2025.102083","DOIUrl":"https://doi.org/10.1016/j.mito.2025.102083","url":null,"abstract":"<p><p>Mitochondrial transcription is key for mitochondrial biogenesis, essential for both gene expression and mtDNA replication. Because of the difficulty of studying the process in vivo, studies of mitochondrial transcription have largely relied on in vitro approaches. Existing methods are based on incorporation of a radioactively labeled nucleotide to facilitate detection of the product while not perturbing the transcription reaction. However, they are difficult to use and cumbersome, preventing their widespread utilization. Here we report a new non-radioactive approach for the in vitro study of mitochondrial transcription that relies on the bio-orthogonal click chemistry reaction, utilizing click-chemistry ready azide-labeled UTP in the mitochondrial transcription system. Our approach recapitulates results obtained using radioactive methods and can be carried out using the reaction conditions typically used for in vitro radioactivity assays.</p>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":" ","pages":"102083"},"PeriodicalIF":4.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206883","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":"COXFA4L3 enhances mitochondrial complex IV function to boost ATP synthesis and drive sperm motility","authors":"Reiji Tokito ,&nbsp;Kosei Oishi ,&nbsp;Tomoya Sugiyama ,&nbsp;Yusuke Fujisawa ,&nbsp;Fujino Kuba ,&nbsp;Kaito Yoshida ,&nbsp;Kaoru Yoshida ,&nbsp;Manabu Yoshida ,&nbsp;Yoichiro Tanaka ,&nbsp;Taku Amo ,&nbsp;Noritaka Yamaguchi ,&nbsp;Taishin Akiyama ,&nbsp;Yuji Imai ,&nbsp;Kazuto Yoshimi ,&nbsp;Tsuyoshi Koide ,&nbsp;Yasuyuki Kurihara","doi":"10.1016/j.mito.2025.102082","DOIUrl":"10.1016/j.mito.2025.102082","url":null,"abstract":"<div><div>COXFA4L3 is a testis-specific cytochrome <em>c</em> oxidase subunit that enhances mitochondrial complex IV activity during spermatogenesis. From the analysis of <em>Coxfa4l3</em> knockout mice, the isoform switch from COXFA4 to COXFA4L3 may increase the potential COX activity, although this activity does not appear in the testis. This latent enhancement becomes evident in sperm, where COXFA4L3 promotes higher respiratory capacity, increasing sperm motility and ATP production. These findings indicate that COXFA4L3 is a key regulator of mitochondrial energy metabolism and may provide insights into the mechanisms underlying male infertility.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"86 ","pages":"Article 102082"},"PeriodicalIF":4.5,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200210","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 DNA variants in normal skins: Insights into prevalent pathogenic variants and quality control surveillance","authors":"Kohta Nakamura ,&nbsp;Yasunari Sato ,&nbsp;Masao Hashimoto ,&nbsp;Naoyuki Matsumoto ,&nbsp;Sachiko Nitta ,&nbsp;Yasushi Okazaki ,&nbsp;Yasuo Miyoshi ,&nbsp;Hiroki Nagase","doi":"10.1016/j.mito.2025.102081","DOIUrl":"10.1016/j.mito.2025.102081","url":null,"abstract":"<div><div>Mitochondrial genome diversity in normal tissues remains poorly understood due to 100 to 1000 copies of mitochondrial DNA in a cell. This study analyzed mitochondrial DNA variants in two distant sites of normal skin tissues from 119 breast surgery cases using deep sequencing. We identified 1337 variants across the mitochondrial genome (59.1 % in coding region). Intriguingly variants were categorized two groups, homoplasmic (81.1 %) or low heteroplasmy rate group (14.1 %). Even MITOMAP pathogenic variants, two out of eight were homoplasmic, common in several patients, and found in both skin sites of the same individual, while six heteroplasmic pathogenic variants were identified in a single patient with &lt; 5 % heteroplasmy rates, half only detected in a single skin site with &lt; 2 % rates. Pathogenic mutations predicted by AlphaMissense were significantly less common in the homoplasmic group (30/1085) but more common in the heteroplasmic group (216/431). Significant increases of mitochondrial copy number were also repeatedly detected in cases with pathogenic variants. This study provides new insights into the diversity of mitochondrial genome and the complexity of mitochondrial homeostasis in normal skin tissue, including the possibility of evading pathogenic mutations through quality control surveillance and the restoration of mitochondrial function due to increase in copy number.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102081"},"PeriodicalIF":4.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040666","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":"Pearson syndrome with atypical presentation of short stature and atypical limb proportions – First reported case in Slovakia","authors":"Gabriela Bľandová ,&nbsp;Michaela Murgašová ,&nbsp;Adam Markocsy ,&nbsp;Marian Baldovič ,&nbsp;Gabriela Krasňanská ,&nbsp;Vladimír Eliaš ,&nbsp;Vanda Repiská ,&nbsp;Michal Konečný","doi":"10.1016/j.mito.2025.102079","DOIUrl":"10.1016/j.mito.2025.102079","url":null,"abstract":"<div><div>In this case report, we describe an individual with Pearson syndrome, representing the first reported case in Slovakia. The patient was 1.5-year-old boy with pancytopenia including macrocytic anemia, neutropenia and thrombocytopenia, pancreatic insufficiency, hepatopathy, psychomotor development delay, short stature and failure to thrive. The patient also had atypical symptoms for Pearson syndrome, including atypical limb proportions and facial dysmorphism, which contributed to the delay in correct diagnosis. In the whole exome sequencing (WES) analysis, virtual panels targeting genes associated with inborn errors of immunity and anemia were selected based on the patient’s clinical phenotype, however no pathogenic variant was identified within these panels. During the evaluation of secondary findings, a pathogenic deletion, m.10952_15371del, was detected in mitochondrial DNA in a heteroplasmic state (55.8% in peripheral blood), leading to the diagnosis. Subsequently, MLPA analysis confirmed this deletion in other patient tissues (urine, bone marrow aspirate, buccal swab) with the highest level of heteroplasmy (70%) detected in the urine sample. Our study emphasizes the importance of a comprehensive diagnostic approach, including the analysis of several tissues, especially in the diagnosis of clinically complex mitochondrial diseases.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102079"},"PeriodicalIF":4.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887593","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":"The homoplasmic MT-TK m.8357T > C mtDNA variant as a cause of multiorgan mitochondrial disease","authors":"Luisa Zupin ,&nbsp;Valeria Capaci ,&nbsp;Maria Teresa Bonati ,&nbsp;Eleonora Lamantea ,&nbsp;Muhammad Suleman ,&nbsp;Andrea Marsala ,&nbsp;Fulvio Celsi ,&nbsp;Beatrice Spedicati ,&nbsp;Sergio Crovella ,&nbsp;Giulia Gortani ,&nbsp;Giorgia Girotto ,&nbsp;Irene Bruno ,&nbsp;Massimo Zeviani","doi":"10.1016/j.mito.2025.102080","DOIUrl":"10.1016/j.mito.2025.102080","url":null,"abstract":"<div><div>The diagnosis of disorders associated with mitochondrial DNA (mtDNA) variants presents substantial complexity due to their genetic and clinical heterogeneity, which is largely influenced by mtDNA heteroplasmy. However, the level of heteroplasmy alone is often not sufficient to predict the clinical phenotype including its severity and progression.</div><div>This study concerns the characterization of the m.8357T &gt; C variant in the <em>MT-TK</em> gene, encoding for mt-tRNA-Lys found in two pediatric siblings. Both had symptoms suggestive of a mitochondrial disease, including severe hearing loss, easy fatigability, decreased activity of mitochondrial complex I in muscle samples, epilepsy, metabolic acidosis with hyperkalemia, and mild kidney impairment.</div><div>The m.8357T &gt; C mtDNA variant was homoplasmic in muscle, blood, urine and fibroblasts. Immortalized fibroblasts from the patients showed reduced activity of mitochondrial complexes I, III and IV, decreased mitochondrial respiration, and abnormal depolarization of the mitochondrial membrane potential. The mt-tRNA-Lys levels were reduced as compared to the mt-tRNA-Leu (UUR) or the snRNA encoded by <em>RNU6B</em> nuclear gene; the level of three mitochondrial DNA encoded proteins was decreased, altogether suggesting a defective translation machinery in cells carrying the variant. Consistently, fibroblasts from the mother, who had only mild hearing loss, despite high level of heteroplasmy, showed some biochemical abnormalities, however milder than in her daughter and son. Contrariwise, their maternal aunt, who showed intellectual disability, mild hearing loss, easy fatigability and weakness was also virtually homoplasmic for the m.8357T &gt; C in blood and urinary sediment cells. These findings suggest the pathogenicity of the m.8357T &gt; C variant but only in condition of homoplasmy.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102080"},"PeriodicalIF":4.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902252","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":"Computational discovery of novel SIRT4 inhibitors for cardiac hypertrophy treatment","authors":"Vaishnavi Jena,&nbsp;B Aparna Naidu,&nbsp;Deepak Sharma,&nbsp;Praisy Joy Bell I,&nbsp;Rajiniraja Muniyan","doi":"10.1016/j.mito.2025.102076","DOIUrl":"10.1016/j.mito.2025.102076","url":null,"abstract":"<div><div>Cardiac hypertrophy is characterized by the enlargement of the heart muscle, often resulting from conditions such as hypertrophic cardiomyopathy (HCM) and physiological hypertrophy. SIRT4 plays a crucial role in cardiac hypertrophy, primarily through its regulation of oxidative stress and mitochondrial function. Therefore, downregulating SIRT4 could help slow the progression of cardiac hypertrophy. This study investigates novel therapeutic approaches for cardiac hypertrophy through various computational strategies, such as Virtual screening, ADMET predictions, molecular docking, and molecular dynamics simulations, to identify potential drug candidates, DB12561 (Hit2), that could inhibit the SIRT4 protein.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102076"},"PeriodicalIF":4.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865230","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":"Outlier maternal haplogroups N5 and X2 and their potential role in elevated tuberculosis prevalence among the Sahariya tribe","authors":"Debashruti Das ,&nbsp;Prajjval Pratap Singh ,&nbsp;Shailesh Desai ,&nbsp;Rahul Kumar Mishra ,&nbsp;Pankaj Shrivastava ,&nbsp;Prashanth Suravajhala ,&nbsp;Rakesh Tamang ,&nbsp;Gyaneshwer Chaubey","doi":"10.1016/j.mito.2025.102078","DOIUrl":"10.1016/j.mito.2025.102078","url":null,"abstract":"<div><div>India bears the largest burden of tuberculosis (TB) cases in the world. Prior studies have highlighted significantly higher pulmonary TB among the Sahariya tribal population in Central India. The disease susceptibility of a population to disease may be influenced by genetic ancestry. In this context, we investigated the maternal genetic ancestry of the Sahariya in relation to their neighbouring tribal populations. For this study, we used the largest available dataset (n = 729), comprising 140 Sahariya individuals and 589 individuals from adjacent caste and tribal groups (including 50 newly sequenced samples). Our detailed mtDNA analysis revealed the exclusive presence of two rare haplogroups N5 and X2 which are completely absent in neighbouring tribal and caste populations. Further examination of the phylogeographic origins of the branches of haplogroups N5 and X2 suggests that these unique founder haplogroup branches (N5a and X2a) were likely introduced into the Sahariya from the western regions of the Indian subcontinent. The temporal expansion of these haplogroups indicates a gene flow from the western area to the Sahariya population during the early Iron Age. In addition to that, we have also analysed 33 SNPs for six TB-associated genes. We observed a single SNP (rs4958847-<em>IRGM1</em>) where the minor allele frequency was significantly different in Sahariya with their neighbouring populations. Consequently, our analysis of maternal genetic ancestry and known associated autosomal genes provides insights that may help explain the higher prevalence of TB among the Sahariya compared to their neighbouring populations.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102078"},"PeriodicalIF":4.5,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883186","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":"Mitotherapy Restores mitochondrial function and improves cognitive deficits in Alzheimer’s disease","authors":"Tulika Gupta ,&nbsp;Asha Rao ,&nbsp;Veena Devi ,&nbsp;Lalita Kumari ,&nbsp;Akshita Negi ,&nbsp;Munish Kumar ,&nbsp;Ranjana Bharti ,&nbsp;Bikash Medhi","doi":"10.1016/j.mito.2025.102077","DOIUrl":"10.1016/j.mito.2025.102077","url":null,"abstract":"<div><div>Mitochondrial dysfunction is a hallmark of Alzheimer’s disease (AD), contributing to cognitive decline. This study explores the therapeutic potential of mitochondrial transplantation in mitigating cognitive decline in AD. Structurally and functionally characterized mitochondria from young rat brains were intravenously transplanted into AD rats. Confocal imaging confirmed integration of exogenous tagged mitochondria into hippocampal tissue. Post-mitotherapy, we noted significant cognitive improvement by neurobehavioral tests and significant reduction in protein levels of amyloid precursor protein. Further mitochondrial functional parameters improved; reduced oxidative stress, improved mitochondrial membrane potential, and calcium homeostasis. These findings highlight mitotherapy as a promising strategy for treating Alzheimer’s disease.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102077"},"PeriodicalIF":4.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874150","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":"Role of Prohibitins as Guardians of mitochondrial homeostasis","authors":"Sabrina Champsi,&nbsp;David A. Hood","doi":"10.1016/j.mito.2025.102075","DOIUrl":"10.1016/j.mito.2025.102075","url":null,"abstract":"<div><div>Mitochondria are complex organelles critical to the maintenance of cellular homeostasis. Central to this regulation are Prohibitins (PHBs), a novel set of proteins involved in several mitochondrial quality control pathways, including protein folding, biogenesis, and mitophagy. PHBs mediate various cellular responses including cell survival and myogenesis, suggesting that their roles are intricate and multifaceted. While evidence suggests that PHBs facilitate mitochondrial homeostasis, their exact mechanism of action remains unclear. Elucidating the precise mechanisms driving PHB-mediated adaptations will ultimately enable the development of therapeutic strategies aimed towards the treatment of age-related diseases, characterized by mitochondrial perturbations.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102075"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753790","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}