Mitochondrion最新文献_第3页

The mitochondrial protein TMEM177 fine-tunes mammalian cytochrome c oxidase assembly 线粒体蛋白TMEM177微调哺乳动物细胞色素c氧化酶组装。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-01-01 Epub Date: 2025-11-16 DOI: 10.1016/j.mito.2025.102099

Jakob D. Busch , Thomas Schöndorf , Dusanka Milenkovic , Xinping Li , Rolf Wibom , Joana F. Silva-Rodrigues , Roberta Filograna , Camilla Koolmeister , Nils-Göran Larsson , Diana Rubalcava-Gracia

{"title":"The mitochondrial protein TMEM177 fine-tunes mammalian cytochrome c oxidase assembly","authors":"Jakob D. Busch , Thomas Schöndorf , Dusanka Milenkovic , Xinping Li , Rolf Wibom , Joana F. Silva-Rodrigues , Roberta Filograna , Camilla Koolmeister , Nils-Göran Larsson , Diana Rubalcava-Gracia","doi":"10.1016/j.mito.2025.102099","DOIUrl":"10.1016/j.mito.2025.102099","url":null,"abstract":"<div><div>The mitochondrial cytochrome <em>c</em> oxidase (COX, complex IV), a multi-subunit protein complex, plays a crucial role in cellular respiration by reducing oxygen to water and simultaneously pumping protons to enable oxidative phosphorylation (OXPHOS). Thus, defects in its assembly can directly affect cellular energy homeostasis. COX20 is an essential chaperone for the core subunit COX2. In human cultured cells, TMEM177 was found to stabilize COX20 and maintain balanced COX2 levels. In mice, TMEM177 was also identified as an interactor of mitochondrial ribosomes. To understand the function of TMEM177 <em>in vivo</em>, we generated <em>Tmem177</em> knockout mice. Here, we analyze how TMEM177 loss affects mitochondrial gene expression, as well as the activity and assembly of OXPHOS complexes. We found that a small proportion of the knockout mice died perinatally, while surviving knockout mice tended to gain less weight. TMEM177 depletion moderately reduced COX20 levels, but OXPHOS complexes were preserved. Moreover, <em>Tmem177</em> and <em>Surf1</em> double knockout mice were born asymptomatic. In conclusion, TMEM177 fine-tunes complex IV assembly by stabilizing COX20 <em>in vivo</em>. Our findings refine the current model of complex IV assembly in mammals.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"86 ","pages":"Article 102099"},"PeriodicalIF":4.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549301","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}

引用次数: 0

Intravenous mitochondrial transplantation as an adjunctive therapy for dilated cardiomyopathy 静脉线粒体移植作为扩张型心肌病的辅助治疗。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-01-01 Epub Date: 2025-11-11 DOI: 10.1016/j.mito.2025.102097

Tuğba Varlik , Didem Algan , Öner Sönmez , Keshav K. Singh , Öner Ülger , Gökhan Burçin Kubat , Jørgen Koch , Zeki Yilmaz

{"title":"Intravenous mitochondrial transplantation as an adjunctive therapy for dilated cardiomyopathy","authors":"Tuğba Varlik , Didem Algan , Öner Sönmez , Keshav K. Singh , Öner Ülger , Gökhan Burçin Kubat , Jørgen Koch , Zeki Yilmaz","doi":"10.1016/j.mito.2025.102097","DOIUrl":"10.1016/j.mito.2025.102097","url":null,"abstract":"<div><div>Dilated cardiomyopathy (DCM) is one of the most prevalent myocardial disorders in various animals. The underlying causes of DCM are complex and often involve multiple contributing mechanisms. Mitochondrial dysfunction has been identified as a key factor in the progression of cardiomyocyte apoptosis. We investigated whether the transplantation of healthy mitochondria improves cardiac function by enhancing the contractile function of myocytes. A 6-year-old dog with cardiomyopathy received platelet-derived, viable mitochondria from a healthy donor as adjunctive therapy alongside standard medical management. Mitochondria were isolated from platelets and administered as a single intravenous bolus at a dose of 81,125 μg/mL. This procedure was carried out under continuous ECG and vital signs monitoring. Ventricular systolic function was assessed at multiple intervals using conventional echocardiography and two-dimensional speckle tracking imaging. Our study revealed notable improvement in systolic performance as early as two hours post-transplantation of mitochondria, with enhanced contractility sustained up to 24 h. These studies suggest mitochondrial transplantation may offer a promising intervention or adjunct to conventional treatments for cardiac dysfunction. This report presents the first documented case of intravenous mitochondrial transplantation in canine DCM.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"86 ","pages":"Article 102097"},"PeriodicalIF":4.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513357","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}

引用次数: 0

The evolving landscape of mitochondrial base editing: advances in precision, modeling, and therapeutic potential 线粒体碱基编辑的发展前景：精度、建模和治疗潜力方面的进步

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-01-01 Epub Date: 2025-10-30 DOI: 10.1016/j.mito.2025.102093

Prathamesh Shelke , Sharon Tribhuvan , Ashish Kumar Agrahari , Reshu Saxena

{"title":"The evolving landscape of mitochondrial base editing: advances in precision, modeling, and therapeutic potential","authors":"Prathamesh Shelke , Sharon Tribhuvan , Ashish Kumar Agrahari , Reshu Saxena","doi":"10.1016/j.mito.2025.102093","DOIUrl":"10.1016/j.mito.2025.102093","url":null,"abstract":"<div><div>The recent development of mitochondrial base editors (mitoBEs) has ushered in a transformational time that has overcome some long-standing limitations in the field of mitochondrial genetics. By closely tracing mitoBE development from the earliest tool mitochondria targeted TALENs to the most recent base editing systems that can precisely convert C•G → T•A and A•T → G•C, we review mitoBEs. We describe the development of recent advancements in mitoBEs including the generation of second generation mitoBEs (mitoBEs v2), which have evidence to identify over 70 mouse mtDNA mutations comparable to human pathogenic variants. Notably, in order to incorporate circular RNA (circRNA) as a delivery vector the editing efficiency has been increased by over 82 %, without experimental evidence of off-target effects. Taking advantage of these gains in technology, these mouse models of mitochondrial diseases, including those associated with Leigh syndrome and LHN, are highly faithful. These models have also confirmed that these specific mtDNA variants have pathological phenotypic evaluations, and have compared to previous editing strategies, mitoBEs v2 have demonstrated improved specificity, stability and safety. We finally discuss the future of mitochondrial base editing and outline the ways it will move forward towards therapeutic potentials in the treatment of the mitochondrial disorders and also in precision medicine.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"86 ","pages":"Article 102093"},"PeriodicalIF":4.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418618","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}

引用次数: 0

Mitochondrial-ER crosstalk: An emerging mechanism in the pathophysiology of pulmonary arterial hypertension 线粒体-内质网串扰：肺动脉高压病理生理的新机制。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-01-01 Epub Date: 2025-11-10 DOI: 10.1016/j.mito.2025.102094

Gauri Chaturvedi , Nandini Dubey , Pranav Panchbhai , Satnam Singh , Ravinder Singh , Upendra Baitha , Neeraj Parakh , Rajiv Narang , Harlokesh Narayan Yadav

{"title":"Mitochondrial-ER crosstalk: An emerging mechanism in the pathophysiology of pulmonary arterial hypertension","authors":"Gauri Chaturvedi , Nandini Dubey , Pranav Panchbhai , Satnam Singh , Ravinder Singh , Upendra Baitha , Neeraj Parakh , Rajiv Narang , Harlokesh Narayan Yadav","doi":"10.1016/j.mito.2025.102094","DOIUrl":"10.1016/j.mito.2025.102094","url":null,"abstract":"<div><div>Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by hyperproliferation and remodeling of the pulmonary vasculature, primarily affecting pulmonary arterial smooth muscle cells (PASMCs) and pulmonary arterial endothelial cells (PAECs). Although several pharmacological agents target the known signaling pathways in these cells, current therapies fail to reverse vascular remodeling, underscoring the urgent need for novel therapeutic strategies. Recent research has shifted focus towards intracellular organelles, specifically mitochondria and the endoplasmic reticulum (ER), as potential therapeutic targets. A key area of interest is mitochondria-associated membranes (MAMs), specialized contact sites between mitochondria and the ER that regulate essential cellular processes, including calcium homeostasis, ER stress signaling, autophagy, and insulin signaling. This review explores the emerging role of MAMs in the pathogenesis of PAH, detailing the molecular players involved in MAM formation and function. Emphasis is placed on identifying MAM-associated proteins that are dysregulated in PASMCs and PAECs, providing insights into their potential as novel therapeutic targets in PAH.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"86 ","pages":"Article 102094"},"PeriodicalIF":4.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505737","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}

引用次数: 0

Mitochondrial Transcription: A click-chemistry derived detection methodology forgoing the use of radiation in in vitro analyses 线粒体转录：一种点击化学衍生的检测方法，放弃在体外分析中使用辐射。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-01-01 Epub Date: 2025-09-29 DOI: 10.1016/j.mito.2025.102083

Anthony Stapon , Miguel Garcia-Diaz

引用次数: 0

COXFA4L3 enhances mitochondrial complex IV function to boost ATP synthesis and drive sperm motility COXFA4L3增强线粒体复合体IV功能，促进ATP合成，驱动精子活力。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-01-01 Epub Date: 2025-09-28 DOI: 10.1016/j.mito.2025.102082

Reiji Tokito , Kosei Oishi , Tomoya Sugiyama , Yusuke Fujisawa , Fujino Kuba , Kaito Yoshida , Kaoru Yoshida , Manabu Yoshida , Yoichiro Tanaka , Taku Amo , Noritaka Yamaguchi , Taishin Akiyama , Yuji Imai , Kazuto Yoshimi , Tsuyoshi Koide , Yasuyuki Kurihara

引用次数: 0

Pearson syndrome with atypical presentation of short stature and atypical limb proportions – First reported case in Slovakia 皮尔逊综合征与矮小的非典型表现和非典型肢体比例-第一例报告在斯洛伐克

IF 4.5 3区生物学

Mitochondrion Pub Date : 2025-11-01 Epub Date: 2025-08-18 DOI: 10.1016/j.mito.2025.102079

Gabriela Bľandová , Michaela Murgašová , Adam Markocsy , Marian Baldovič , Gabriela Krasňanská , Vladimír Eliaš , Vanda Repiská , Michal Konečný

{"title":"Pearson syndrome with atypical presentation of short stature and atypical limb proportions – First reported case in Slovakia","authors":"Gabriela Bľandová , Michaela Murgašová , Adam Markocsy , Marian Baldovič , Gabriela Krasňanská , Vladimír Eliaš , Vanda Repiská , Michal Konečný","doi":"10.1016/j.mito.2025.102079","DOIUrl":"10.1016/j.mito.2025.102079","url":null,"abstract":"<div><div>In this case report, we describe an individual with Pearson syndrome, representing the first reported case in Slovakia. The patient was 1.5-year-old boy with pancytopenia including macrocytic anemia, neutropenia and thrombocytopenia, pancreatic insufficiency, hepatopathy, psychomotor development delay, short stature and failure to thrive. The patient also had atypical symptoms for Pearson syndrome, including atypical limb proportions and facial dysmorphism, which contributed to the delay in correct diagnosis. In the whole exome sequencing (WES) analysis, virtual panels targeting genes associated with inborn errors of immunity and anemia were selected based on the patient’s clinical phenotype, however no pathogenic variant was identified within these panels. During the evaluation of secondary findings, a pathogenic deletion, m.10952_15371del, was detected in mitochondrial DNA in a heteroplasmic state (55.8% in peripheral blood), leading to the diagnosis. Subsequently, MLPA analysis confirmed this deletion in other patient tissues (urine, bone marrow aspirate, buccal swab) with the highest level of heteroplasmy (70%) detected in the urine sample. Our study emphasizes the importance of a comprehensive diagnostic approach, including the analysis of several tissues, especially in the diagnosis of clinically complex mitochondrial diseases.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"85 ","pages":"Article 102079"},"PeriodicalIF":4.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial quality control in exercise-mitigated muscular atrophy. 运动缓解性肌萎缩的线粒体质量控制。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2025-11-01 Epub Date: 2025-07-28 DOI: 10.1016/j.mito.2025.102074

Jingcheng Fan, Xin Wen, Xuemei Duan, Xinyi Zhu, Jianzheng Bai, Tan Zhang

引用次数: 0

Targeted mitochondrial metabolism for anti-tumor therapy 靶向线粒体代谢抗肿瘤治疗

IF 4.5 3区生物学

Mitochondrion Pub Date : 2025-11-01 Epub Date: 2025-07-27 DOI: 10.1016/j.mito.2025.102073

Chi Yan , Xuefang Li , Pei Wei , Xiaoyan Zhang , Haining Wang , Zhigang Chen , Fei Lin , Guangjian Lu

{"title":"Targeted mitochondrial metabolism for anti-tumor therapy","authors":"Chi Yan , Xuefang Li , Pei Wei , Xiaoyan Zhang , Haining Wang , Zhigang Chen , Fei Lin , 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":"2025-11-01","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}

引用次数: 0

Novel mutations in MTERF3: First report of a new genetic cause in two Chinese patients with developmental delay, intermittent hypoglycemia and metabolic acidosis MTERF3的新突变：首次报道了两名中国发育迟缓、间歇性低血糖和代谢性酸中毒患者的新遗传原因。

IF 3.9 3区生物学

Mitochondrion Pub Date : 2025-11-01 Epub Date: 2025-06-19 DOI: 10.1016/j.mito.2025.102059

Ruoyu Duan , Refiloe Laurentinah Mahlatsi , Ya Wang , Chaolong Xu , Mingzhao Wang , Zhuo Zou , Zhimei Liu , Huafang Jiang , Xin Duan , Jie Deng , Minhan Song , Yun Liu , Hezhi Fang , JianXin Lyu , Fang Fang

{"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 , Refiloe Laurentinah Mahlatsi , Ya Wang , Chaolong Xu , Mingzhao Wang , Zhuo Zou , Zhimei Liu , Huafang Jiang , Xin Duan , Jie Deng , Minhan Song , Yun Liu , Hezhi Fang , JianXin Lyu , 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 > T p.(Pro352Leu) in Patient 1, and a homozygous variant c.943A > 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":"2025-11-01","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}

引用次数: 0