Mitochondrion
· 2026 Jan · PMID 41033386
·
Publisher ↗
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...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.
Tokito R, Oishi K, Sugiyama T
… +13 more, Fujisawa Y, Kuba F, Yoshida K, Yoshida K, Yoshida M, Tanaka Y, Amo T, Yamaguchi N, Akiyama T, Imai Y, Yoshimi K, Koide T, Kurihara Y
Mitochondrion
· 2026 Jan · PMID 41027500
·
Publisher ↗
COXFA4L3 is a testis-specific cytochrome c oxidase subunit that enhances mitochondrial complex IV activity during spermatogenesis. From the analysis of Coxfa4l3 knockout mice, the isoform switch from COXFA4 to COXFA4L3 m...COXFA4L3 is a testis-specific cytochrome c oxidase subunit that enhances mitochondrial complex IV activity during spermatogenesis. From the analysis of Coxfa4l3 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.
Nakamura K, Sato Y, Hashimoto M
… +5 more, Matsumoto N, Nitta S, Okazaki Y, Miyoshi Y, Nagase H
Mitochondrion
· 2025 Nov · PMID 40935056
·
Publisher ↗
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 tiss...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 < 5 % heteroplasmy rates, half only detected in a single skin site with < 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.
Jena V, Naidu BA, Sharma D
… +2 more, Bell PJ, Muniyan R
Mitochondrion
· 2025 Nov · PMID 40834968
·
Publisher ↗
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...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.
Bľandová G, Murgašová M, Markocsy A
… +5 more, Baldovič M, Krasňanská G, Eliaš V, Repiská V, Konečný M
Mitochondrion
· 2025 Nov · PMID 40834967
·
Publisher ↗
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 thro...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.
Zupin L, Capaci V, Bonati MT
… +10 more, Lamantea E, Suleman M, Marsala A, Celsi F, Spedicati B, Crovella S, Gortani G, Girotto G, Bruno I, Zeviani M
Mitochondrion
· 2025 Nov · PMID 40834966
·
Publisher ↗
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, t...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. This study concerns the characterization of the m.8357T > C variant in the MT-TK 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. The m.8357T > 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 RNU6B 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 > C in blood and urinary sediment cells. These findings suggest the pathogenicity of the m.8357T > C variant but only in condition of homoplasmy.
Das D, Singh PP, Desai S
… +5 more, Mishra RK, Shrivastava P, Suravajhala P, Tamang R, Chaubey G
Mitochondrion
· 2025 Nov · PMID 40829724
·
Publisher ↗
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 o...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-IRGM1) 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.
Gupta T, Rao A, Devi V
… +5 more, Kumari L, Negi A, Kumar M, Bharti R, Medhi B
Mitochondrion
· 2025 Nov · PMID 40819696
·
Publisher ↗
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...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.
Fan J, Wen X, Duan X
… +3 more, Zhu X, Bai J, Zhang T
Mitochondrion
· 2025 Nov · PMID 40738240
·
Publisher ↗
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 ar...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.
Mitochondrion
· 2025 Nov · PMID 40738239
·
Publisher ↗
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 pathwa...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.
Maison DP, Khadka VS, Mohd-Ibrahim I
… +4 more, Peluso MJ, Henrich TJ, Deng Y, Gerschenson M
Mitochondrion
· 2025 Nov · PMID 40738238
·
Full text
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 foll...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.
Yan C, Li X, Wei P
… +5 more, Zhang X, Wang H, Chen Z, Lin F, Lu G
Mitochondrion
· 2025 Nov · PMID 40730267
·
Publisher ↗
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 d...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.
Lee KCY, Williams AL, Fujimoto A
… +7 more, Gerschenson M, Schuller C, Polgar N, Alfulaij N, Shimada BK, Seale LA, Shohet RV
Mitochondrion
· 2025 Nov · PMID 40706825
·
Full text
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 cardiomyo...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. Indirect calorimetry suggested similar whole-body metabolism of PKM2 knockout (PKM2) and control (PKM2) 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 females, while male PKM2 mice fed a HFD were comparatively leaner than their PKM2 counterparts. 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.
Mitochondrion
· 2025 Nov · PMID 40691914
·
Publisher ↗
UNLABELLED: 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 acco...UNLABELLED: 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. HYPOTHESIS: MT-SNVs contribute to the unexplained heritability of CAD and may also be associated with lifestyle behaviours. METHODS: We analysed 203 high-quality common and low-frequency MT-SNVs (minor allele frequency > 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. RESULTS: Several MT-SNVs were nominally associated with the CAD status and lifestyle habits, including m.10873T > C (MT-ND4 gene), m.15301G > A (MT-CYB gene), m.8701A > G (MT-ATP6 gene), and m.9540T > C (MT-CO3). After adjusting for covariates, these associations did not remain statistically significant. CAD status was significantly but weakly correlated (|r| < 0.2) with 64 dietary preferences of the 108 lifestyle traits (Bonferroni-adjusted P < 0.05), indicating modest but widespread dietary pattern differences. CONCLUSIONS: 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.
Zioudi A, Gouiza I, Galai S
… +11 more, Hechmi M, Klaa H, Miladi Z, Ben Younes T, Benrhouma H, Ben Youssef-Turki I, Omar S, Lenaers G, Kefi R, Gouider-Khouja N, Kraoua I
Mitochondrion
· 2025 Nov · PMID 40653181
·
Publisher ↗
Mitochondrial Neuro-Gastro-Intestinal Encephalopathy (MNGIE) is a rare and fatal mitochondrial disorder caused by biallelic mutations in the TYMP gene. In rare cases, it can be caused by pathogenic variants in the POLG g...Mitochondrial Neuro-Gastro-Intestinal Encephalopathy (MNGIE) is a rare and fatal mitochondrial disorder caused by biallelic mutations in the TYMP gene. In rare cases, it can be caused by pathogenic variants in the POLG gene, with a clinical presentation similar to that of TYMP-related MNGIE, except for the absence of leukoencephalopathy. 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 POLG variant c.2391G > T (p.Met797Ile), which may suggest a founder effect.
Duan R, Mahlatsi RL, Wang Y
… +12 more, Xu C, Wang M, Zou Z, Liu Z, Jiang H, Duan X, Deng J, Song M, Liu Y, Fang H, Lyu J, Fang F
Mitochondrion
· 2025 Nov · PMID 40543543
·
Publisher ↗
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...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 MTERF3 knockdown HEK293 cell line was generated, followed by rescue experiments with wild-type and mutant MTERF3. Two patients mainly presented with developmental delay. Genetic testing identified compound heterozygous variants c.635dup p.(Asn212Lysfs*7) and c.1055C > T p.(Pro352Leu) in Patient 1, and a homozygous variant c.943A > Gp.(Met315Val) in Patient 2. Patient's fibroblasts and MTERF3 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 MTERF3 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.
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 peroxi...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 (HO)-induced mitochondrial damage in porcine oocytes and restore their developmental competence. Oocytes were exposed to HO 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.
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 m...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 ex vivo 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.
Kuo CW, Chen HA, Hsu RH
… +14 more, Wu CS, Hsu C, Lee MJ, Chien YH, Hsueh HW, Yang FJ, Fan PC, Weng WC, Lin RJ, Chen TC, Yang CC, Lee WT, Hwu WL, Lee NC
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...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.
Huang Q, Shire D, Hollis F
… +5 more, Abuaish S, Picard M, Monk C, Duman EA, Trumpff C
Mitochondrion
· 2025 Sep · PMID 40473185
·
Full text
BACKGROUND: 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 str...BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 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 < 0.05). CONCLUSIONS: 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.