Mitochondrial Communications最新文献

{"title":"Homoplasmic MT-TG m.9997T>C variant associated with hypertrophic cardiomyopathy: Pathogenicity and genotype–phenotype analysis","authors":"Jianing Wang,&nbsp;Jiayin Wang,&nbsp;Busu Li,&nbsp;Xiaojing Zhu,&nbsp;Yan Lin,&nbsp;Ying Zhao,&nbsp;Weiyue Si,&nbsp;Yuying Zhao,&nbsp;Chuanzhu Yan,&nbsp;Kunqian Ji","doi":"10.1016/j.mitoco.2026.06.001","DOIUrl":"10.1016/j.mitoco.2026.06.001","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial cardiomyopathy (MCM), a common subtype of mitochondrial disorders accounting for 20-40% of cases, presents significant diagnostic and therapeutic challenges due to genetic heterogeneity and variable clinical phenotypes.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive analysis of the clinical, histopathological, molecular, and genetic characteristics of a 23-year-old male with maternally inherited hypertrophic cardiomyopathy (HCM) associated with the homoplasmic m.9997 T &gt; C variant.</div></div><div><h3>Results</h3><div>The patient exhibited early-onset exercise intolerance, arrhythmias, and cardiac dysfunction. Cardiac Magnetic Resonance Imaging confirmed asymmetric HCM with left ventricular enlargement. Genetic analysis identified a homoplasmic m.9997T &gt; C variant across multiple tissues (blood, urine, mucosa, muscle). Muscle biopsy revealed typical mitochondrial abnormalities, and reduced expression of complex IV subunits.</div></div><div><h3>Conclusion</h3><div>Our findings support the pathogenic association of the homoplasmic m.9997T &gt; C variant in HCM and highlight the clinical significance of homoplasmic mtDNA mutations in tissue-specific mitochondrial disorders, contributing to the broader understanding of homoplasmic mutations in mitochondrial disease.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"4 ","pages":"Pages 10-15"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148656757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the role of mitochondrial homeostasis in hepatocellular carcinoma initiation and progression: Mechanisms and therapeutic opportunities","authors":"Jiashun Xu,&nbsp;Xinlei Meng,&nbsp;Ming Gong,&nbsp;Ensong Sun,&nbsp;Jianwei Sun,&nbsp;Hayam Hamdy,&nbsp;Junling Shen,&nbsp;Hui Li","doi":"10.1016/j.mitoco.2026.07.002","DOIUrl":"10.1016/j.mitoco.2026.07.002","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is an aggressive malignancy characterized by profound metabolic reprogramming, mitochondrial dysfunction, and resistance to both conventional and immune-based therapies. Mitochondria play a central role in HCC development by coordinating bioenergetics, redox balance, mitochondrial dynamics, quality control, and immunometabolic signaling.</div><div>Accumulating evidence indicates that disruption of mitochondrial fission, fusion, and mitophagy promotes tumor growth, metastasis, and therapeutic resistance through metabolic remodeling and adaptive stress responses. Enhanced mitochondrial fission, largely mediated by DRP1 and its associated adaptors, favors glycolytic reprogramming, reactive oxygen species (ROS) accumulation, and invasive behavior, whereas impaired fusion compromises oxidative phosphorylation efficiency.</div><div>Alterations in mitochondrial DNA (mtDNA) integrity and nucleoid organization further exacerbate mitochondrial dysfunction. These changes can trigger inflammatory signaling through cytosolic mtDNA release and contribute to remodeling of the tumor microenvironment. Mitophagy exhibits context-dependent roles in HCC: it may suppress tumor initiation by removing damaged mitochondria, yet under stress conditions such as hypoxia or nutrient deprivation, it supports tumor survival and adaptation.</div><div>Beyond tumor-intrinsic effects, mitochondrial metabolism plays a key role in shaping the tumor immune microenvironment. It regulates immunometabolism, antigen presentation, ROS signaling, and immune cell differentiation, thereby influencing immune evasion and responsiveness to immunotherapy.</div><div>Collectively, mitochondrial pathways are emerging as actionable targets for overcoming immunosuppression and therapeutic resistance. This review integrates current knowledge on mitochondrial dynamics, metabolism, mtDNA regulation, mitophagy, and immunometabolic crosstalk in HCC, and discusses emerging strategies to exploit mitochondrial vulnerabilities for improved clinical outcomes.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"4 ","pages":"Pages 27-39"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148934974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial NMNAT3 reduces amyloid aggregates in Drosophila and alters the amyloid processing in the 3xTgAD mouse","authors":"Zhu Yi ,&nbsp;Naynika Juvvadi ,&nbsp;Grace Zhai ,&nbsp;Carlos T. Moraes ,&nbsp;Milena Pinto","doi":"10.1016/j.mitoco.2026.01.001","DOIUrl":"10.1016/j.mitoco.2026.01.001","url":null,"abstract":"<div><div>Alzheimer's disease is a progressive neurological disorder characterized by two main neuropathological hallmarks: neurofibrillary tangles and amyloid plaques. Both are protein aggregates, composed mainly of hyperphosphorylated Tau and the amyloid fragment Aβ, respectively. NMNAT (Nicotinamide mononucleotide adenylyltransferase) is an endogenous enzyme involved in the conversion of NMN to NAD. It is known for its neuroprotective functions, particularly against axonal degeneration. We have previously shown that different isoforms of NMNAT can protect cells from neurotoxic stress caused by protein aggregates by acting as chaperones. Accordingly, the mitochondrial-localized isoform NMNAT3 exhibits potent chaperone activity, which antagonizes the aggregation of a wide spectrum of pathological amyloid client proteins in culture, including Tau and amyloid beta. Although mostly cytosolic, Aβ has also been detected in mitochondria and mitochondrial membranes. To investigate whether NMNAT3 could serve as a neuroprotective factor in amyloid pathology <em>in vivo</em>, we overexpressed NMNAT3 in two different models: a <em>Drosophila</em> model overexpressing APP and PS1 in developing photoreceptors, and the 3xTg-AD mouse, in which NMNAT3 was expressed in forebrain neurons and which accumulates neurofibrillary tangles and plaques in the hippocampus and cortex. When expressed in the <em>Drosophila</em> eye, APP accumulated in a location- and time-dependent manner, and co-expression of NMNAT3 decreased the total number of aggregates. When expressed in the mouse brain, NMNAT3 did not affect amyloid plaque number or volume; nonetheless, it altered APP processing, leading to the accumulation of oligomers and soluble C-terminal fragments. We conclude that the effects of NMNAT3 on APP differ between models, likely due to differences in access to the sites of protein aggregation and the neuronal environments between flies and mice.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"4 ","pages":"Pages 1-9"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146135775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial reprogramming as a central driver of pancreatic ductal adenocarcinoma","authors":"Jed Allyn T. Hernandez,&nbsp;Prycelline M. Abedejos,&nbsp;Kianna Denise F. Lopez,&nbsp;Alessandra Beatrice L. Donado,&nbsp;Mariel Denise A. Roque,&nbsp;Kirsten Ysabelle V. Serranilla,&nbsp;Ju Eun Seol,&nbsp;Jessa E. Flores,&nbsp;Maria Victoria Faith V. Garcia,&nbsp;Jubert C. Marquez,&nbsp;Jin Han","doi":"10.1016/j.mitoco.2026.07.001","DOIUrl":"10.1016/j.mitoco.2026.07.001","url":null,"abstract":"<div><div>Pancreatic cancer has recently been observed to have a rise in incidence and prevalence in terms of cancer-related mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent type of pancreatic cancer and is considered highly aggressive. Although recent advancements in chemotherapy, radiation therapy, and immunotherapy provide increased options for treatment, the survival rate of pancreatic cancer compared to other types of malignancies is still relatively low. Especially for PDAC, surgical resection is the only curative therapy considered, but most of these tumors are diagnosed at an advanced stage and are therefore ineligible for surgery. Emerging evidence demonstrates that mitochondrial reprogramming is a central driver of PDAC progression, influencing metabolic plasticity, redox balance, mitochondrial dynamics, and therapy resistance. This review discusses how mitochondrial changes promote PDAC and emerging therapies targeting mitochondria, particularly those that modulate mitochondrial function and metabolism. A deeper understanding of mitochondrial reprogramming may provide novel biomarkers and therapeutic opportunities, ultimately improving early detection and treatment outcomes in PDAC.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"4 ","pages":"Pages 16-26"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148730550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dynamic changes and energy surplus","authors":"Kaiyue Wu,&nbsp;Shuang Shen","doi":"10.1016/j.mitoco.2025.11.001","DOIUrl":"10.1016/j.mitoco.2025.11.001","url":null,"abstract":"<div><div>Mitochondrial homeostasis is essential for cell survival and metabolic balance. This review systematically examines the molecular mechanisms, pathological correlations, and regulatory relationships among three major processes: mitochondrial homeostasis, lipoacylation modification, and mitochondrial overheating (excess energy). Mitochondrial dynamic balance adapts to energy demands through division mediated by Drp1, as well as regulation by Mfn1/2 and OPA1 for fusion. Lipoacylation activates PDH and α-KGDHC, which ensures metabolic efficiency and reduces ROS. Overheating characterized by increased ATP/ADP ratios, an enhanced ETC reducing state, and ROS accumulation, disrupts the first two processes and creates a vicious cycle. This network disorder is a common pathological basis for neurodegenerative diseases (such as CMT2A, AD), cardiovascular diseases (such as dilated cardiomyopathy), and metabolic diseases (such as type 2 diabetes and NAFLD). However, the details of these sensing pathways regulation remain unclear and require further investigation. This review aims to provide a theoretical framework for researching and treating diseases related to mitochondrial dysfunction.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 90-95"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the influence of mitochondrial Ca2+ regulation on neurodegenerative disease progression","authors":"Jianxu Sun ,&nbsp;Ge Gao ,&nbsp;Sitong Wang ,&nbsp;Hongmei Liu ,&nbsp;Tie-Shan Tang","doi":"10.1016/j.mitoco.2025.01.001","DOIUrl":"10.1016/j.mitoco.2025.01.001","url":null,"abstract":"<div><div>Mitochondria are pivotal hubs in maintaining cellular homeostasis, encompassing vital processes such as bioenergetics, redox regulation, Ca²⁺ signaling, and programmed cell death. Ca²⁺ is a key second messenger within cells, paramount in numerous critical biological processes. The maintenance of mitochondrial calcium homeostasis relies on a delicate balance between Ca²⁺ uptake and efflux. At the mitochondrial level, Ca²⁺ serves a dual function, participating in essential physiological processes such as ATP production and the regulation of mitochondrial metabolisms and contributing to pathophysiological events, including cell death and cancer metastasis. Alterations in mitochondrial Ca²⁺ (Ca²⁺_mito) levels influence cellular activity and functionality. The regulation of mitochondrial Ca²⁺ homeostasis involves the collaborative participation of the mitochondrial Ca²⁺ transporter and the mitochondria-endoplasmic reticulum contact sites (MERCS). This review provides a comprehensive overview of current knowledge regarding the regulation of mitochondrial Ca²⁺ homeostasis and its implications in both physiological processes and neurodegenerative disorders. Moreover, we highlight potential opportunities and challenges in developing therapeutic interventions that target mitochondrial Ca²⁺ homeostasis and its regulators, such as novel drug delivery systems and specific calcium-modulating agents.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 1-15"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143139404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial heterogeneity: within and between cells","authors":"Shiyuan Chen ,&nbsp;Jiangbin Ye ,&nbsp;Zhenglong Gu","doi":"10.1016/j.mitoco.2025.03.002","DOIUrl":"10.1016/j.mitoco.2025.03.002","url":null,"abstract":"","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 52-53"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the oncogenic impact of heteroplasmic de novo MT-ND5 truncating mutations","authors":"Yuanyuan Wu ,&nbsp;Jiangbin Ye ,&nbsp;Zhenglong Gu","doi":"10.1016/j.mitoco.2025.03.001","DOIUrl":"10.1016/j.mitoco.2025.03.001","url":null,"abstract":"<div><div>Numerous mitochondrial DNA (mtDNA) variants are associated with cancers, yet the causal link remains inconclusive. Using DddA-derived cytosine base editors, we induced <em>de novo</em> truncating mutations in <em>MT-ND5</em> in HEK293 cells, establishing heteroplasmy, the coexistence of mutant and wild-type mtDNA. This study aimed to investigate the full molecular etiology following these deleterious mtDNA mutations, particularly in oncogenesis. We found that low to moderate heteroplasmic levels of the mutants were sufficient to impair mitochondrial functions and alter cellular redox status. Cellular adaptation to elevated ROS (Reactive Oxygen Species), energy crisis, and altered redox status was observed across varying heteroplasmy levels. Increased oncogenic potential was confirmed through <em>in vitro</em> oncogenesis and <em>in vivo</em> xenograft assays. Transcriptomic analysis revealed upregulated migration, invasion, and genome instability pathways, and downregulated ROS scavenging pathways. Our results demonstrate that <em>MT-ND5</em> mutations drive cancer progression by increasing cellular ROS and genome instability, and by altering the redox balance and epigenetic landscapes.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 26-43"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleotide imbalance fuels ageing-associated inflammation","authors":"Tao Long,&nbsp;Da Jia,&nbsp;Lin Zhao","doi":"10.1016/j.mitoco.2025.11.002","DOIUrl":"10.1016/j.mitoco.2025.11.002","url":null,"abstract":"","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 96-98"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are patients with mitochondrial diseases prone to inflammatory and immune dysfunction: A scoping review and retrospective chart analysis","authors":"Eiti Rautela ,&nbsp;Savannah Sauve ,&nbsp;Nikki Kovac ,&nbsp;Edana Cassol ,&nbsp;David Dyment ,&nbsp;Martin Holcik","doi":"10.1016/j.mitoco.2025.03.003","DOIUrl":"10.1016/j.mitoco.2025.03.003","url":null,"abstract":"<div><div>Mitochondrial diseases (MDs) are a significant patient burden and are linked to the dysregulation of various metabolic processes and cellular energy production. Additionally, mitochondria play a central role in regulating immune function and inflammatory response. This study aimed to examine the connection between MD and immune dysfunction, including inflammation as a specific immune response to infection. A scoping literature review and retrospective chart review were conducted. The scoping review followed the five-stage methodology framework by Arksey and O'Malley, extracting 1823 articles from PubMed using Covidence as managing software, with full texts of 10 articles analyzed. A retrospective patient chart review was conducted on 92 patients with a confirmed diagnosis of MD from the Children's Hospital of Eastern Ontario. The scoping review identified cases of MDs associated with inflammation, including individuals with POLG-associated disease. Immune dysfunction was observed in a subset of complex MDs, particularly in individuals with biallelic variation in POLGF and ATAD3A, who had a heavy burden of disease. The results from both the scoping and retrospective chart reviews suggest an association between complex MD and altered inflammatory and immune functions.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 16-25"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}