Mitochondrion最新文献

{"title":"Peripheral immune progression to long COVID is associated with mitochondrial gene transcription: A meta-analysis","authors":"David P. Maison ,&nbsp;Vedbar S. Khadka ,&nbsp;Isam Mohd-Ibrahim ,&nbsp;Michael J. Peluso ,&nbsp;Timothy J. Henrich ,&nbsp;Youping Deng ,&nbsp;Mariana Gerschenson","doi":"10.1016/j.mito.2025.102072","DOIUrl":"10.1016/j.mito.2025.102072","url":null,"abstract":"<div><div>SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has led to millions of cases of Long COVID worldwide. Long COVID is a phenomenon characterized by persistent and debilitating mental and physical symptoms following acute infection. Despite ongoing research, trials, and considerable progress in understanding Long COVID, its exact causes remain only partially understood, with current hypotheses addressing specific aspects of the condition. We conducted one of the most comprehensive meta-analyses to date of all quality bulk RNA-seq studies worldwide from the COVID-19 pandemic and show significant mitochondrial transcript changes in the peripheral immune system of people with Long COVID, with unexpectedly low levels of intracellular viral RNA in Long COVID. This extensive analysis, which includes 26 studies and 1,272 individuals, shows that mononuclear cells, PBMC, and granulocytes from Long COVID patients exhibit significant alterations in mitochondrial genes and related processes. These findings likely represent the true transcriptomic landscape of Long COVID across diverse datasets, highlighting the long-lasting impacts of SARS-CoV-2 on peripheral immune function. In combination with other ex vivo and proteomics studies showing mitochondrial dysfunction, our results suggest critical new directions, such as the potential role of clonal hematopoiesis and infected seed cells. This work highlights the need for further investigation into the mechanisms underlying these immune changes and persistent symptoms in people with Long COVID. These findings will serve as a foundation for defining the paradigm underlying the biological mechanisms of Long COVID, driving research into the peripheral immune system, bone marrow, and mitochondria.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102072"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723345","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":"Targeted mitochondrial metabolism for anti-tumor therapy","authors":"Chi Yan ,&nbsp;Xuefang Li ,&nbsp;Pei Wei ,&nbsp;Xiaoyan Zhang ,&nbsp;Haining Wang ,&nbsp;Zhigang Chen ,&nbsp;Fei Lin ,&nbsp;Guangjian Lu","doi":"10.1016/j.mito.2025.102073","DOIUrl":"10.1016/j.mito.2025.102073","url":null,"abstract":"<div><div>Cancer has become a focal point of concern owing to its escalating incidence and mortality rates. However, traditional treatment modalities are encumbered by inherent constraints, posing ongoing challenges in achieving definitive cancer eradication. Mitochondria, crucial for cellular growth and physiological homeostasis, manifest distinctive structural and metabolic alterations within cancerous cells compared to their normal counterparts. Targeting aberrant mitochondrial metabolism in tumor cells has emerged as a promising therapeutic strategy, capitalizing on the precision, efficacy, and minimal adverse effects associated with targeted therapeutic approaches. However, due to the complexity of tumor cells, the specific mechanism underlying the role of mitochondria in tumor development and new anti-tumor drugs targeting mitochondrial metabolism still need to be further studied. This review focuses on studies that target mitochondrial DNA, oxidative phosphorylation, mitochondrial energy metabolism, and amino acid metabolism in tumor cells, elucidating the methods involved in targeting mitochondrial metabolism and underscoring the significance of future studies in developing therapies targeting mitochondrial metabolism for cancer treatment.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102073"},"PeriodicalIF":4.5,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739619","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":"PKM2 is a key regulator of cardiac lipid metabolism in mice","authors":"Katie C.Y. Lee ,&nbsp;Allison L. Williams ,&nbsp;Anastasia Fujimoto ,&nbsp;Mariana Gerschenson ,&nbsp;Connor Schuller ,&nbsp;Noemi Polgar ,&nbsp;Naghum Alfulaij ,&nbsp;Briana K. Shimada ,&nbsp;Lucia A. Seale ,&nbsp;Ralph V. Shohet","doi":"10.1016/j.mito.2025.102070","DOIUrl":"10.1016/j.mito.2025.102070","url":null,"abstract":"<div><div>Deficiencies in lipid metabolism can have severe consequences for cardiac function. We previously showed that regulating glucose flux by pyruvate kinase 2 (PKM2) affects lipid synthesis and droplet abundance in cardiomyocytes. This study aims to examine how PKM2 regulates lipid metabolism in the heart.</div><div>Indirect calorimetry suggested similar whole-body metabolism of PKM2 knockout (PKM2^-/-) and control (PKM2^fl/fl) young mice (2–3 months), but indicated that lipids were utilized to a greater degree in aged (1-year) PKM2^-/- mice compared to controls. Metabolic chamber studies also revealed an overall negative energy balance that contributed to reduced exercise tolerance in aged PKM2^-/- mice. Metabolomics showed substantially lower carnitine levels in PKM2^-/- cardiomyocyte fractions (CM), alongside increased circulating and cardiac dicarboxylic acids, as well as reduced mitochondrial palmitate oxidation in PKM2^-/- CM. We also noted a sex-specific difference in which female PKM2^-/- mice exhibited greater high-fat diet (HFD)-induced hyperglycemia and weight gain compared to PKM2^fl/fl females, while male PKM2^-/- mice fed a HFD were comparatively leaner than their PKM2^fl/fl counterparts.</div><div>PKM2^-/- mice have aberrations in lipid metabolism that worsen with age, shifting whole-body metabolism towards a preference for lipid utilization. This may lead to a decline in aerobic capacity during exercise in aged PKM2^-/- mice. PKM2^-/- CM also display compromised mitochondrial lipid metabolism due to carnitine deficiency. Challenging PKM2^-/- mice with a HFD revealed sex-dependent differences in glycemic control and body weight. Our results indicate a role for PKM2 in sustaining the homeostasis of cardiac and whole-body lipid metabolism that contributes to overall physiological fitness.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102070"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708131","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":"Comprehensive analysis of the mitochondrial DNA variants using multivariate covariate and multiple-testing models to enhance reliability reveals potential associations with coronary artery disease traits and dietary preferences","authors":"Aniket Sawant ,&nbsp;Irina Griķe ,&nbsp;Baiba Vilne","doi":"10.1016/j.mito.2025.102069","DOIUrl":"10.1016/j.mito.2025.102069","url":null,"abstract":"<div><div>Coronary Artery Diseases (CAD) contribute significantly to the global morbidity and mortality. While genome-wide association studies have identified numerous nuclear genomic variants linked to CAD, these account for less than 20 % of the disease’s estimated heritability (variation in disease risk attributed to genetic factors), suggesting the potential contribution of non-nuclear genetic elements, such as mitochondrial single-nucleotide variants (MT-SNVs). MT-SNVs may also influence lifestyle-related traits, which often interact with genetic predisposition to modulate CAD risk.</div><div>Hypothesis: MT-SNVs contribute to the unexplained heritability of CAD and may also be associated with lifestyle behaviours.</div></div><div><h3>Methods</h3><div>We analysed 203 high-quality common and low-frequency MT-SNVs (minor allele frequency &gt; 0.01) in 20,400 CAD cases (myocardial infarction and/or revascularisation) from the UK Biobank after rigorous quality control and imputation. Associations between MT-SNVs and 85 quantitative food intake traits (FIQTs) and 23 established CAD risk factors (e.g., smoking status, lipid levels, physical activity) using both Frequentist and Bayesian methods. Correlation analyses were performed across these 108 lifestyle behaviours.</div></div><div><h3>Results</h3><div>Several MT-SNVs were nominally associated with the CAD status and lifestyle habits, including m.10873T &gt; C (MT-ND4 gene), m.15301G &gt; A (MT-CYB gene), m.8701A &gt; G (MT-ATP6 gene), and m.9540T &gt; C (MT-CO3). After adjusting for covariates, these associations did not remain statistically significant. CAD status was significantly but weakly correlated (|r| &lt; 0.2) with 64 dietary preferences of the 108 lifestyle traits (Bonferroni-adjusted P &lt; 0.05), indicating modest but widespread dietary pattern differences.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that MT-SNVs may explain some of the CAD heritability. However, larger cohorts with more comprehensive mitochondrial data are needed to clarify their potential role.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102069"},"PeriodicalIF":4.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682791","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":"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}