Mitochondrion最新文献

{"title":"A Tunisian POLG mutation expands the clinical spectrum of POLG-related disorders","authors":"Abir Zioudi ,&nbsp;Ismail Gouiza ,&nbsp;Said Galai ,&nbsp;Meriem Hechmi ,&nbsp;Hedia Klaa ,&nbsp;Zouhour Miladi ,&nbsp;Thouraya Ben Younes ,&nbsp;Hanene Benrhouma ,&nbsp;Ilhem Ben Youssef-Turki ,&nbsp;Souheil Omar ,&nbsp;Guy Lenaers ,&nbsp;Rym Kefi ,&nbsp;Neziha Gouider-Khouja ,&nbsp;Ichraf Kraoua","doi":"10.1016/j.mito.2025.102071","DOIUrl":"10.1016/j.mito.2025.102071","url":null,"abstract":"<div><div>Mitochondrial Neuro-Gastro-Intestinal Encephalopathy (MNGIE) is a rare and fatal mitochondrial disorder caused by biallelic mutations in the <em>TYMP</em> gene. In rare cases, it can be caused by pathogenic variants in the <em>POLG</em> gene, with a clinical presentation similar to that of <em>TYMP</em>-related MNGIE, except for the absence of leukoencephalopathy.</div><div>Here we report the cases of six Tunisian patients presenting with a homogeneous clinical MNGIE-like phenotype, characterized by an early infantile onset. Key features included psychomotor delay or regression, peripheral neuropathy, gastrointestinal disturbances, hypotrophy or growth retardation, and elevated cerebrospinal fluid protein levels. All patients originated from the same governorate and carried the same homozygous <em>POLG</em> variant c.2391G &gt; T (p.Met797Ile), which may suggest a founder effect.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102071"},"PeriodicalIF":3.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626698","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":"Novel mutations in MTERF3: First report of a new genetic cause in two Chinese patients with developmental delay, intermittent hypoglycemia and metabolic acidosis","authors":"Ruoyu Duan ,&nbsp;Refiloe Laurentinah Mahlatsi ,&nbsp;Ya Wang ,&nbsp;Chaolong Xu ,&nbsp;Mingzhao Wang ,&nbsp;Zhuo Zou ,&nbsp;Zhimei Liu ,&nbsp;Huafang Jiang ,&nbsp;Xin Duan ,&nbsp;Jie Deng ,&nbsp;Minhan Song ,&nbsp;Yun Liu ,&nbsp;Hezhi Fang ,&nbsp;JianXin Lyu ,&nbsp;Fang Fang","doi":"10.1016/j.mito.2025.102059","DOIUrl":"10.1016/j.mito.2025.102059","url":null,"abstract":"<div><div>MTERF3, a negative regulator of mtDNA transcription, was first identified in 2007.Recent studies have revealed the pivotal role of MTERF3 throughout the entire lifecycle of mtDNA. However, no disease phenotypes have been linked to this gene till now. Genetic testing was performed on two unrelated families. Mitochondrial respiration and OXPHOS complex activity were assessed in patient-derived fibroblasts. An <em>MTERF3</em> knockdown HEK293 cell line was generated, followed by rescue experiments with wild-type and mutant <em>MTERF3</em>. Two patients mainly presented with developmental delay. Genetic testing identified compound heterozygous variants c.635dup p.(Asn212Lysfs*7) and c.1055C &gt; T p.(Pro352Leu) in Patient 1, and a homozygous variant c.943A &gt; Gp.(Met315Val) in Patient 2. Patient’s fibroblasts and <em>MTERF3</em> knockdown cells showed impaired mitochondrial respiration and reduced levels of OXPHOS complexes I, III, and IV. Transcription of MT-ND5, ND6, COII, and COIII was reduced, while other mitochondrial genes were upregulated. Wild-type <em>MTERF3</em> expression restored these defects, but the variant Pro352Leu from patient failed to rescue mitochondrial dysfunction. This study identifies a novel mitochondrial disease phenotype and establishes the first association with MTERF3, expanding the mitochondrial disease spectrum and offering insights into the clinical relevance of the MTERF family.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102059"},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340244","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":"Chlordecone (kepone) induces mitochondrial dysfunction in human cardiac tissue","authors":"Alexia FUNDERE ,&nbsp;Marie-Daniela DUBOIS ,&nbsp;Magalie VATIN INAMO ,&nbsp;Fatima RADOUANI ,&nbsp;Prisca JALTA ,&nbsp;Dabor RESIERE ,&nbsp;Remi NEVIERE","doi":"10.1016/j.mito.2025.102058","DOIUrl":"10.1016/j.mito.2025.102058","url":null,"abstract":"<div><div>Chlordecone exposure in humans has been associated with increased incidence of prostate cancer, impaired fertility, and fetal/perinatal abnormalities while experiment rodent studies suggest that chlordecone can inhibit magnesium-ATPase, little is known about its mitochondrial toxicity in humans. Our objective was to test whether chlordecone would induce mitochondrial dysfunction in human cardiac cells in <em>ex vivo</em> heart preparations. Biopsies of human atrial tissue were obtained during cannulation for cardiopulmonary bypass from patients who were undergoing programmed cardiac surgery for coronary artery bypass. Cardiac preparations were incubated with vehicle or chlordecone (5 nM and 50 nM) for 24 hr followed by mitochondrial high-resolution oxygraphy studies. Compared with vehicle, chlordecone cardiac exposure at the concentrations of 5 nM and 50 nM impaired mitochondrial respiratory rates. Chlordecone concentrations of 5 nM and 50 nM similarly increased state 2 respiration rate and maximal respiration capacity with no change of state 3 (ADP) respiration rate, which suggests the uncoupling of between mitochondrial oxidative phosphorylation and electron transport through the respiratory chain complexes. In conclusion, our study suggests that chlordecone at clinically relevant concentration impairs mitochondrial function leading to uncoupling, which may induce abnormal cardiac cell responses, including aberrant calcium handling and oxidative stress.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102058"},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340243","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":"Ultrastructural and functional recovery of mitochondria and improved developmental competence by melatonin in oxidatively stressed porcine oocytes","authors":"Heyyoung Kim ,&nbsp;Seonggyu Bang ,&nbsp;Ayeong Han ,&nbsp;Heejae Kang ,&nbsp;Islam M. Saadeldin ,&nbsp;Ahmad Yar Qamar ,&nbsp;Sanghoon Lee ,&nbsp;Jongki Cho","doi":"10.1016/j.mito.2025.102060","DOIUrl":"10.1016/j.mito.2025.102060","url":null,"abstract":"<div><div>Mitochondrial dysfunction induced by oxidative stress impairs oocyte maturation and subsequent embryonic development. In this study, we investigated whether melatonin, a potent antioxidant, could mitigate hydrogen peroxide (H₂O₂)-induced mitochondrial damage in porcine oocytes and restore their developmental competence. Oocytes were exposed to H₂O₂ prior to in vitro maturation (IVM), followed by treatment with varying concentrations of melatonin (0, 0.5, 1, and 5 μM). Melatonin treatment significantly improved maturation and blastocyst formation rates, with 1 μM showing the most pronounced effect. This recovery was accompanied by enhanced mitochondrial bioenergetics, which was likely driven by reduced ROS accumulation and increased intracellular glutathione. Melatonin also reversed the ultrastructural abnormalities of mitochondria, reduced apoptotic signals, and normalized mitophagy markers. These findings suggest that melatonin confers mitochondrial protection and promotes oocyte competence under oxidative stress, supporting its therapeutic potential in reproductive biotechnology.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102060"},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338361","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":"Machine learning to predict mitochondrial diseases by phenotypes","authors":"Chieh-Wen Kuo ,&nbsp;Hui-An Chen ,&nbsp;Rai-Hseng Hsu ,&nbsp;Chao-Szu Wu ,&nbsp;Ching Hsu ,&nbsp;Ming-Jen Lee ,&nbsp;Yin-Hsiu Chien ,&nbsp;Hsueh-Wen Hsueh ,&nbsp;Feng-Jung Yang ,&nbsp;Pi-Chuan Fan ,&nbsp;Wen-Chin Weng ,&nbsp;Ru-Jen Lin ,&nbsp;Ta-Ching Chen ,&nbsp;Chih-Chao Yang ,&nbsp;Wang-Tso Lee ,&nbsp;Wuh-Liang Hwu ,&nbsp;Ni-Chung Lee","doi":"10.1016/j.mito.2025.102061","DOIUrl":"10.1016/j.mito.2025.102061","url":null,"abstract":"<div><div>Diagnosing mitochondrial diseases remains challenging because of the heterogeneous symptoms. This study aims to use machine learning to predict mitochondrial diseases from phenotypes to reduce genetic testing costs. This study included patients who underwent whole exome or mitochondrial genome sequencing for suspected mitochondrial diseases. Clinical phenotypes were coded, and machine learning models (support vector machine, random forest, multilayer perceptron, and XGBoost) were developed to classify patients. Of 103 patients, 43 (41.7%) had mitochondrial diseases. Myopathy and respiratory failure differed significantly between the two groups. XGBoost achieved the highest accuracy (67.5%). In conclusion, machine learning improves patient prioritization and diagnostic yield.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102061"},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329618","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 health, prenatal distress, and gestational age: investigation of cf-mtDNA and GDF15 in two pregnancy studies from the USA and Turkey","authors":"Qiuhan Huang ,&nbsp;David Shire ,&nbsp;Fiona Hollis ,&nbsp;Sameera Abuaish ,&nbsp;Martin Picard ,&nbsp;Catherine Monk ,&nbsp;Elif Aysimi Duman ,&nbsp;Caroline Trumpff","doi":"10.1016/j.mito.2025.102057","DOIUrl":"10.1016/j.mito.2025.102057","url":null,"abstract":"<div><h3>Background</h3><div>Pregnancy outcomes are influenced by maternal distress but the pathways underlying these effects are still unknown. Mitochondria, crucial for energy production and stress adaptation, may link psychosocial stress to its biological effects, especially during pregnancy when energy demands significantly increase. This study explores two mitochondrial markers-circulating cell-free mitochondrial DNA (cf-mtDNA) and Growth Differentiation Factor-15 (GDF15)-as potential mitochondrial health indicators linking maternal distress to pregnancy outcomes in two longitudinal studies from the USA and Turkey.</div></div><div><h3>Methods</h3><div>We analyzed biological, demographic, and psychological data from women in two pregnancy studies: EPI (N = 187, USA) and BABIP (N = 198, Turkey). Data were collected at multiple timepoints during the perinatal period, including late 2nd and 3rd trimester, with EPI also including additional data at early 2nd trimester and 4–14 months postpartum. Prenatal maternal psychological distress was measured as perceived stress, anxiety, and depressive symptoms. Plasma cf-mtDNA and GDF15 levels were assessed using qPCR and ELISA, respectively. Statistical analyses included Wilcoxon signed-rank tests, Spearman correlations, and Mann-Whitney tests.</div></div><div><h3>Results</h3><div>Plasma cf-mtDNA levels did not significantly vary across pregnancy, while plasma GDF15 levels increased from early to late pregnancy and decreased postpartum. Late 2nd trimester plasma GDF15 was negatively correlated with pre-pregnancy BMI (p = 0.035) and gestational age (p = 0.0048) at birth. Early 2nd trimester maternal distress was associated with lower cf-mtDNA (all p-values &lt; 0.05) and a trend for lower GDF15. Higher pre-pregnancy BMI and late-pregnancy maternal distress were linked to smaller postpartum GDF15 declines in EPI (all p-values &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>This study identified distinct patterns of plasma cf-mtDNA and GDF15 levels during the perinatal period across studies from two countries, linking these mitochondrial markers to maternal distress and pregnancy outcomes.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102057"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234520","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":"Targeting mitochondrial quality control for myocardial ischemia-reperfusion injury","authors":"Yuxuan He ,&nbsp;Sixu Ren ,&nbsp;Chenglin Liu ,&nbsp;Xiufen Zheng ,&nbsp;Cuilin Zhu","doi":"10.1016/j.mito.2025.102046","DOIUrl":"10.1016/j.mito.2025.102046","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) remains the leading global cause of mortality. Acute myocardial infarction (AMI) refers to acute myocardial ischemia resulting from thrombosis secondary to coronary atherosclerosis, which poses a major threat to human health. Clinically, timely revascularization (reperfusion) represents the basis of clinical treatment for AMI. However, secondary myocardial ischemia–reperfusion injury (MIRI) caused by reperfusion often exacerbates damage, representing a major challenge in clinical practice. Mitochondria represent essential organelles for maintaining cardiac function and cellular bioenergetics in MIRI. In recent years, the role of mitochondrial quality control (MQC) in maintaining cell homeostasis and mediating MIRI has been extensively studied. This review provides a concise overview of MQC mechanisms at the molecular, organelle, and cellular levels and their possible complex regulatory network in MIRI. In addition, potential treatment strategies targeting MQC to mitigate MIRI are summarized, highlighting the gap between current preclinical research and clinical transformation. Overall, this review provides theoretical guidance for further research and clinical translational studies.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102046"},"PeriodicalIF":3.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147788","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":"Auditory neuropathy spectrum disorder and related auditory features in patients with hearing loss associated with the MT-TS1 m.7471dup variant","authors":"Shujiro Minami ,&nbsp;Amina Kida ,&nbsp;Satomi Inoue ,&nbsp;Haruka Murakami ,&nbsp;Noriko Morita ,&nbsp;Akira Takagi ,&nbsp;Takeshi Usui ,&nbsp;Tomoko Sugiuchi ,&nbsp;Kazuki Yamazawa ,&nbsp;Kiyomitsu Nara ,&nbsp;Hideki Mutai ,&nbsp;Tatsuo Matsunaga","doi":"10.1016/j.mito.2025.102056","DOIUrl":"10.1016/j.mito.2025.102056","url":null,"abstract":"<div><div>The m.7471dup variant of mitochondrial-tRNA Ser (UCN) (<em>MT-TS1</em>) is associated with sensorineural hearing loss (SNHL), neurological abnormalities, or both. Phenotypic variations in SNHL associated with the m.7471dup variant were the focus of our investigation. Five Japanese families carrying the variant were subjected to comprehensive genetic and clinical evaluations and audiometric testing. Notably, two families presented with auditory neuropathy spectrum disorder (ANSD), and two other families presented with auditory brainstem response thresholds much higher than those expected from the pure-tone audiometry results, which is analogous to ANSD. This is the first study to demonstrate that the m.7471dup variant can be associated with ANSD or similar characteristics. The penetrance of the m.7471dup variant was 71.4 % overall, with 100 % penetrance in cases with homoplasmy and 42.9 % penetrance in cases with heteroplasmy. Disease onset was congenital or early onset (≤ 6 years) in 80 % of the patients. The hearing levels ranged from normal to profound, and four subjects presented with neurological or psychiatric abnormalities. About 80 % of subjects who had newborn hearing screening passed the screening, suggesting late-onset or progressive hearing loss. These findings underscore the importance of rigorous follow-up evaluations, genetic counseling, and evaluation of educational environment considerations for patients carrying the m.7471dup variant.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102056"},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128152","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":"Corrigendum to “In vitro studies in VCP-associated multisystem proteinopathy suggest altered mitochondrial bioenergetics” [Mitochondrion 22 (2015) 1–8]","authors":"Angèle Nalbandian ,&nbsp;Katrina J. Llewellyn ,&nbsp;Arianna Gomez ,&nbsp;Naomi Walker ,&nbsp;Hailing Su ,&nbsp;Andrew Dunnigan ,&nbsp;Marilyn Chwa ,&nbsp;Jouni Vesa ,&nbsp;M.C. Kenney ,&nbsp;Virginia E. Kimonis","doi":"10.1016/j.mito.2025.102044","DOIUrl":"10.1016/j.mito.2025.102044","url":null,"abstract":"","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102044"},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032731","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":"Urolithin-A supplementation alleviates sepsis-induced acute lung injury by reducing mitochondrial dysfunction and modulating macrophage polarization","authors":"Mohd Mohsin ,&nbsp;Almaz Zaki ,&nbsp;Gulnaz Tabassum ,&nbsp;Salman Khan ,&nbsp;Shakir Ali ,&nbsp;Tanveer Ahmad ,&nbsp;Mansoor Ali Syed","doi":"10.1016/j.mito.2025.102047","DOIUrl":"10.1016/j.mito.2025.102047","url":null,"abstract":"<div><div>Sepsis is a severe and life-threatening condition marked by excessive inflammation, mitochondrial dysfunction, and epithelial barrier disruption, often leading to Acute Lung Injury (ALI). Mitophagy, a cellular mechanism that removes damaged mitochondria, plays a vital role in maintaining mitochondrial health during sepsis. In this study, we investigated the protective effects of Urolithin-A against ALI and sepsis. In LPS-stimulated RAW264.7 macrophages, Urolithin-A significantly reduced mitochondrial dysfunction, Reactive Oxygen Species (ROS), Nitric Oxide (NO) production, and apoptosis. Additionally, it enhanced mitophagy by upregulating PINK1, Parkin, and LC3-II, which helped preserve mitochondrial function.</div><div>In vivo, Urolithin-A treatment in mouse models of ALI and sepsis reduced lung injury and inflammation, as shown by improved ALI scores, decreased wet/dry lung weight ratios, and lower levels of inflammatory markers such as iNOS, IL-1β, and MPO. Urolithin-A also improved epithelial barrier integrity and upregulated anti-apoptotic markers, demonstrating its ability to alleviate sepsis-induced lung damage. These findings suggest that Urolithin-A holds significant promise as a therapeutic agent for managing inflammatory lung conditions associated with sepsis.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102047"},"PeriodicalIF":3.9,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928111","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}