Mitochondrial Communications最新文献

Decoding the influence of mitochondrial Ca2+ regulation on neurodegenerative disease progression

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

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

Are patients with mitochondrial diseases prone to inflammatory and immune dysfunction: A scoping review and retrospective chart analysis

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

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

Nature conference on mitochondria and immunity: Uncovering Mitochondria–Immunity crosstalk and fostering global scientific exchanges

Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.12.002

Juan Liu, Yanjun Li, Yushan Zhu, Quan Chen

引用次数: 0

Lipid transfer at mitochondrial membrane contact sites

Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.11.002

Qingzhu Chu , Wei-Ke Ji

引用次数: 0

Innovative methods for isolating highly purified mitochondria essential for biomedical studies 分离生物医学研究必需的高纯度线粒体的创新方法

Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.09.002

Yan Huang , Xiangwaner Jin , Yi Zhang , Yanan Li, Jinming Liu, Yanjun Li

{"title":"Innovative methods for isolating highly purified mitochondria essential for biomedical studies","authors":"Yan Huang , Xiangwaner Jin , Yi Zhang , Yanan Li, Jinming Liu, Yanjun Li","doi":"10.1016/j.mitoco.2024.09.002","DOIUrl":"10.1016/j.mitoco.2024.09.002","url":null,"abstract":"<div><div>Mitochondria, being multifunctional and highly complex organelles, possess unique structures and exhibit heterogeneity. In recent decades, the isolation and purification of functional mitochondria have been instrumental for mitochondrial research. As mitochondrial research, including omics, advances, there is a growing demand for the isolation of highly purified mitochondria or individual mitochondria. This paper provides a comprehensive overview of the evolution of mitochondrial purification methods and introduces two innovative and improved techniques for isolating mitochondria from mouse cerebral cortex and in vitro cultured cells. The first method utilizes self-prepared magnetic beads conjugated with anti-TOMM20 antibody for the immunoisolation of highly purified intact mitochondria. The second method utilizes flow cytometry to isolate single mitochondria based on fluorescent protein labeling, allowing for the isolation of mitochondria from a highly heterogeneous population. We provide detailed protocols that aim to benefit the rapidly growing mitochondria research community in assessing mitochondrial function, especially at the single-organelle level.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 90-99"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423696","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 lipid metabolism in metastatic breast cancer 转移性乳腺癌的线粒体脂质代谢

Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.07.001

Bhuban Ruidas

{"title":"Mitochondrial lipid metabolism in metastatic breast cancer","authors":"Bhuban Ruidas","doi":"10.1016/j.mitoco.2024.07.001","DOIUrl":"10.1016/j.mitoco.2024.07.001","url":null,"abstract":"<div><p>The significance of mitochondrial lipid metabolism in cancer stemness, survival, and proliferation, particularly in the context of metastasis, has garnered significant attention. Warburg's hypothesis posits that cancer cells primarily rely on aerobic glycolysis for survival due to mitochondrial dysfunction. However, recent evidence has challenged this perspective, emphasizing the direct involvement of mitochondria in cancer's rapid progression. Metabolic rearrangements, a hallmark of metastatic cancer, fulfill heightened energy demands during rapid proliferation, primarily through mitochondrial oxidative phosphorylation and lipid metabolism, even under hypoxic conditions. Moreover, lipid metabolism is elevated throughout the progression of metastatic cancer to meet crucial energy needs. However, the relative importance of mitochondrial lipid metabolism and aerobic glycolysis in highly aggressive cancers remains poorly defined, and further investigation could enhance treatment outcomes in cases of metastatic progression. In this context, a comprehensive understanding of mitochondrial lipid metabolism in metastatic breast cancer patients could potentially lead to significant breakthroughs in improving therapies, especially for triple-negative breast cancer.</p></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 58-66"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590279224000063/pdfft?md5=50183d4ee164426611eb75a5606347dd&pid=1-s2.0-S2590279224000063-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843364","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

The mitochondria chronicles of melatonin and ATP: Guardians of phase separation 褪黑素和 ATP 的线粒体编年史：相分离的守护者

Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.07.002

Doris Loh , Russel J. Reiter

{"title":"The mitochondria chronicles of melatonin and ATP: Guardians of phase separation","authors":"Doris Loh , Russel J. Reiter","doi":"10.1016/j.mitoco.2024.07.002","DOIUrl":"10.1016/j.mitoco.2024.07.002","url":null,"abstract":"<div><p>Phase separation is a thermodynamic process used by all living organisms since the origin of life to rapidly assemble and disassemble membraneless condensates in response to changes in exogenous and endogenous stress conditions. For ∼4.5 billion years, living organisms in the three major domains of life depended upon the high chemical potential of adenosine triphosphate (ATP) to harness nonequilibrium chemical reactions that govern the formation and suppression of membraneless organelles via phase separation. Melatonin enhances the unique chemistry of ATP in water, promoting the solubilization via the adenosine moiety effect, supporting the survival of early organisms in an anoxic environment. Eukaryotes, including dinoflagellates and plants, can produce melatonin in extreme levels under stress as compensation for inadequate ATP for optimal regulation of survival responses dependent upon phase separation. The production of ATP and melatonin in mitochondria enables the fine-tuning of dynamics that modulate phase separation of proteins associated with ATP production, biogenesis and degradation, membrane dynamics, gene transcription, mitophagy, unfolded protein response, and apoptosis/survival responses in mitochondria. Exogenous melatonin application enhances mitochondrial ATP production and synergy, attenuating aberrant phase separation and associated mitochondrial dysfunction and disease.</p></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 67-84"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590279224000075/pdfft?md5=7d5edc08bd32f09b779eb9636af81ee8&pid=1-s2.0-S2590279224000075-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846938","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