Mitochondrial Communications最新文献

Decoding the influence of mitochondrial Ca2+ regulation on neurodegenerative disease progression 解码线粒体Ca2+调节对神经退行性疾病进展的影响

Mitochondrial Communications Pub Date : 2025-01-01 DOI: 10.1016/j.mitoco.2025.01.001

Jianxu Sun , Ge Gao , Sitong Wang , Hongmei Liu , Tie-Shan Tang

{"title":"Decoding the influence of mitochondrial Ca2+ regulation on neurodegenerative disease progression","authors":"Jianxu Sun , Ge Gao , Sitong Wang , Hongmei Liu , 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, Ca<sup>2+</sup> signaling, and programmed cell death. Ca<sup>2+</sup> 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 Ca<sup>2+</sup> uptake and efflux. At the mitochondrial level, Ca<sup>2+</sup> 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 Ca<sup>2+</sup> (Ca<sup>2+</sup><sub>mito</sub>) levels influence cellular activity and functionality. The regulation of mitochondrial Ca<sup>2+</sup> homeostasis involves the collaborative participation of the mitochondrial Ca<sup>2+</sup> transporter and the mitochondria-endoplasmic reticulum contact sites (MERCS). This review provides a comprehensive overview of current knowledge regarding the regulation of mitochondrial Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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}

引用次数: 0

Exploring the oncogenic impact of heteroplasmic de novo MT-ND5 truncating mutations 探索异质新生MT-ND5截断突变对肿瘤的影响

Mitochondrial Communications Pub Date : 2025-01-01 DOI: 10.1016/j.mitoco.2025.03.001

Yuanyuan Wu , Jiangbin Ye , Zhenglong Gu

{"title":"Exploring the oncogenic impact of heteroplasmic de novo MT-ND5 truncating mutations","authors":"Yuanyuan Wu , Jiangbin Ye , 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}

引用次数: 0

Mitochondrial heterogeneity: within and between cells 线粒体异质性：细胞内和细胞间

Mitochondrial Communications Pub Date : 2025-01-01 DOI: 10.1016/j.mitoco.2025.03.002

Shiyuan Chen , Jiangbin Ye , Zhenglong Gu

引用次数: 0

Are patients with mitochondrial diseases prone to inflammatory and immune dysfunction: A scoping review and retrospective chart analysis 线粒体疾病患者是否容易发生炎症和免疫功能障碍：范围回顾和回顾性图表分析

Mitochondrial Communications Pub Date : 2025-01-01 DOI: 10.1016/j.mitoco.2025.03.003

Eiti Rautela , Savannah Sauve , Nikki Kovac , Edana Cassol , David Dyment , Martin Holcik

{"title":"Are patients with mitochondrial diseases prone to inflammatory and immune dysfunction: A scoping review and retrospective chart analysis","authors":"Eiti Rautela , Savannah Sauve , Nikki Kovac , Edana Cassol , David Dyment , 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}

引用次数: 0

Mitochondrial Communications Pub Date : 2025-01-01 DOI: 10.1016/j.mitoco.2025.08.001

Valeria Lobanova , Ivan Kozenkov , Eldar Khaibulin , Maria Tatarkina , Bogdan Efimenko , Viktoria Skripskaya , Akhsarbek H. Dzhigkaev , Anastasia S. Krylova , Anastasia V. Prokopenko , Stepan V. Toshchakov , Andrey Goncharov , Konstantin Popadin , Konstantin V. Gunbin

{"title":"Age-related dynamics of m.189A>G and m.408T>A variants in skeletal muscle of an osteoarthritic Cohort: Connections to BMI and muscle strength","authors":"Valeria Lobanova , Ivan Kozenkov , Eldar Khaibulin , Maria Tatarkina , Bogdan Efimenko , Viktoria Skripskaya , Akhsarbek H. Dzhigkaev , Anastasia S. Krylova , Anastasia V. Prokopenko , Stepan V. Toshchakov , Andrey Goncharov , Konstantin Popadin , Konstantin V. Gunbin","doi":"10.1016/j.mitoco.2025.08.001","DOIUrl":"10.1016/j.mitoco.2025.08.001","url":null,"abstract":"<div><div>The origin and expansion of mitochondrial somatic variants, influenced by tissue-specific mutagenesis and selection, are not well understood despite their relevance to aging and age-related diseases. Postmitotic tissues, such as skeletal muscles, are particularly underexplored, even though mtDNA variant evolution in these tissues can differ significantly from that in proliferative tissues. To address this, we analyzed mitochondrial heteroplasmy in skeletal muscle samples from an osteoarthritic cohort (N = 105). We observed that the age-related dynamics of two famous variants m.189A > G and m.408T > A in our cohort is indistinguishable from their dynamics in random control cohort, suggesting that they are not a cause of muscular problems, but rather mark the age-related processes in muscles. We also observed that when adjusted by age and gender, carriers of these variants tend to have higher BMI, body weight, and muscle strength than non-carriers. Putting together all the lines of evidence, we propose that these variants are able to rapidly expand through selfish dynamics, which is especially pronounced in hypertrophic muscle fibers of individuals with higher body weight. Further investigation is necessary to clarify this hypothesis.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 66-78"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048127","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}

引用次数: 0

Extra-mitochondrial ATP synthesis, proton dynamics at the membrane, and mitochondria-derived vesicles: Current findings and considerations 线粒体外ATP合成，膜上的质子动力学和线粒体衍生的囊泡：目前的发现和考虑

Mitochondrial Communications Pub Date : 2025-01-01 DOI: 10.1016/j.mitoco.2025.06.002

Alessandro Maria Morelli , Ann Saada , Felix Scholkmann

引用次数: 0

Mitochondrial‐derived vesicles: at the crossroads of mitochondrial functions and metabolites 线粒体来源的囊泡：在线粒体功能和代谢物的十字路口

Mitochondrial Communications Pub Date : 2025-01-01 DOI: 10.1016/j.mitoco.2025.06.001

Min Tang , Zhiyin Song , Da Jia

引用次数: 0

In vivo imaging of neuronal mitochondrial Ca2+ transients with two-photon microscopy in awake mice 清醒小鼠神经元线粒体Ca2+瞬态的双光子显微镜在体成像

Mitochondrial Communications Pub Date : 2025-01-01 DOI: 10.1016/j.mitoco.2025.08.002

Shan Qiu , Haoyu Zhang , Fangxu Zhou , Haipeng Huang , Heping Cheng , Xianhua Wang

{"title":"In vivo imaging of neuronal mitochondrial Ca2+ transients with two-photon microscopy in awake mice","authors":"Shan Qiu , Haoyu Zhang , Fangxu Zhou , Haipeng Huang , Heping Cheng , Xianhua Wang","doi":"10.1016/j.mitoco.2025.08.002","DOIUrl":"10.1016/j.mitoco.2025.08.002","url":null,"abstract":"<div><div>Mitochondrial Ca<sup>2+</sup> plays important roles in shaping intracellular Ca<sup>2+</sup> signaling and modulating energy metabolism. Dysregulated mitochondrial Ca<sup>2+</sup> dynamics have been increasingly implicated in the pathogenesis of neurodegenerative disorders. To unravel how mitochondrial Ca<sup>2+</sup> participates in the processes of neural activity and neurodegeneration, it is essential but challenging to monitor its dynamics <em>in vivo</em>. Recent advances in two-photon microscopy and genetically encoded Ca<sup>2+</sup> indicators have enabled high-resolution imaging of mitochondrial Ca<sup>2+</sup> in the brain. Here, we present a comprehensive protocol for <em>in vivo</em> imaging and analysis of mitochondrial Ca<sup>2+</sup> dynamics in neurons of awake mice. This protocol provides detailed methodologies for indicator delivery, chronic cranial window implantation, two-photon imaging, and downstream data analysis. By offering a standardized and reproducible workflow, this protocol aims to facilitate investigation of mitochondrial Ca<sup>2+</sup> dynamics <em>in vivo</em> in both physiological and pathological contexts.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 54-65"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048128","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}

引用次数: 0

Tissue-specific knockdown of OMM protein via GFP nanobody-mediated degradation 通过 GFP 纳米抗体介导的降解，特异性敲除组织中的 OMM 蛋白

Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.07.003

Xiaojie Wang , Qiyue Zhang , Suhong Xu

{"title":"Tissue-specific knockdown of OMM protein via GFP nanobody-mediated degradation","authors":"Xiaojie Wang , Qiyue Zhang , Suhong Xu","doi":"10.1016/j.mitoco.2024.07.003","DOIUrl":"10.1016/j.mitoco.2024.07.003","url":null,"abstract":"<div><p>Mitochondria, with their diverse morphologies across tissues, hint at a unique function based on location. For instance, outer mitochondrial membrane (OMM) proteins are critical for various mitochondrial activities, including regulating mitochondrial dynamics, ion homeostasis, and protein translocation. This study introduces a green fluorescent protein (GFP) nanobody-mediated protein degradation (G-DEG) system to investigate tissue-specific mitochondrial functions in <em>Caenorhabditis elegans</em> and potential other model systems. G-DEG combines CRISPR-Cas9 GFP knock-in with ZIF-1-mediated protein degradation, leveraging the high specificity of antigen–antibody recognition for precise manipulation across species. We demonstrate the G-DEG system by targeting FZO-1, a mammalian homolog of MAN1/2, which is essential for mitochondrial fusion. Our protocol includes CRISPR-Cas9-mediated <em>fzo-1</em>:GFP knock-in and the construction of tissue-specific GFP nanobody degradation plasmids for the epidermis, muscle, and neurons. Injection of these plasmids into wild-type <em>C. elegans</em> and subsequent crossbreeding with the <em>fzo-1</em>:GFP knock-in strain allows for effective FZO-1 targeting, providing tissue-specific insights into mitochondrial protein function. Overall, G-DEG emerges as a powerful and versatile tool for tissue-specific knockdown of OMM proteins, paving the way for advanced studies on their diverse biological functions.</p></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 85-89"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590279224000087/pdfft?md5=f5d2d52b3e5d9bb6460686031c07f0e6&pid=1-s2.0-S2590279224000087-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961581","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}

引用次数: 0

Single-cell mitochondrial DNA sequencing: Methodologies and applications 单细胞线粒体 DNA 测序：方法与应用

Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.10.001

Guoqiang Zhou , Zhenglong Gu , Jin Xu

引用次数: 0