Pub Date : 2025-01-01DOI: 10.1016/j.mitoco.2025.12.003
Du Feng, Quan Chen
{"title":"Powering forward: A year of discovery in mitochondrial science","authors":"Du Feng, Quan Chen","doi":"10.1016/j.mitoco.2025.12.003","DOIUrl":"10.1016/j.mitoco.2025.12.003","url":null,"abstract":"","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages A1-A2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883673","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}
Pub Date : 2025-01-01DOI: 10.1016/j.mitoco.2025.06.002
Alessandro Maria Morelli , Ann Saada , Felix Scholkmann
Adenosine triphosphate (ATP) is essential for almost all life forms. In our article, we discuss (i) insights into the bioenergetics of ATP generation, including an extended view of proton currents during oxidative phosphorylation (OXPHOS), (ii) experimental work showing the ability of several biological structures to perform extra-mitochondrial OXPHOS, (iii) the role of mitochondria-derived vesicles (MDVs) in extra-mitochondrial OXPHOS, and (iv) the relevance of these aspects for the interpretation of the human brain map of mitochondrial density and ATP-synthesizing capacity. In our opinion, extra-mitochondrial OXPHOS and MDVs are important topics for future research that will significantly expand our picture of cellular bioenergetics.
{"title":"Extra-mitochondrial ATP synthesis, proton dynamics at the membrane, and mitochondria-derived vesicles: Current findings and considerations","authors":"Alessandro Maria Morelli , Ann Saada , Felix Scholkmann","doi":"10.1016/j.mitoco.2025.06.002","DOIUrl":"10.1016/j.mitoco.2025.06.002","url":null,"abstract":"<div><div>Adenosine triphosphate (ATP) is essential for almost all life forms. In our article, we discuss (i) insights into the bioenergetics of ATP generation, including an extended view of proton currents during oxidative phosphorylation (OXPHOS), (ii) experimental work showing the ability of several biological structures to perform extra-mitochondrial OXPHOS, (iii) the role of mitochondria-derived vesicles (MDVs) in extra-mitochondrial OXPHOS, and (iv) the relevance of these aspects for the interpretation of the human brain map of mitochondrial density and ATP-synthesizing capacity. In our opinion, extra-mitochondrial OXPHOS and MDVs are important topics for future research that will significantly expand our picture of cellular bioenergetics.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 47-51"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522473","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}
Pub Date : 2025-01-01DOI: 10.1016/j.mitoco.2025.06.001
Min Tang , Zhiyin Song , Da Jia
{"title":"Mitochondrial‐derived vesicles: at the crossroads of mitochondrial functions and metabolites","authors":"Min Tang , Zhiyin Song , Da Jia","doi":"10.1016/j.mitoco.2025.06.001","DOIUrl":"10.1016/j.mitoco.2025.06.001","url":null,"abstract":"","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 44-46"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254734","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}
Pub Date : 2025-01-01DOI: 10.1016/j.mitoco.2025.12.002
Julia G. Martin , Tong Zhan , Deshka L. Neill , Ke Xu , Evan W. Miller
Mitochondria play central roles in the physiology of eukaryotic cells. Mitochondrial membrane potential, in turn, is a key driver of mitochondrial physiology. We previously developed a system to localize voltage-sensitive fluorophores to mitochondria based on the hydrolysis of labile acetoxymethyl (AM) esters. One potential problem with this system is the premature hydrolysis of the labile AM ester prior to accumulation in the mitochondria. A possible solution is to replace the AM ester with a bulky cyclopropylmethylacetoxy (CPM) ester, which resists uncatalyzed hydrolysis but can be removed by certain esterases. When paired with exogenous expression of mitochondrially-targeted esterases like porcine liver esterase (PLE), this chemical-genetic hybrid approach can improve localization to mitochondria. In this manuscript, we use superresolution microscopy to show that a variety of proteins, including esterases from pig and bacteria can be effectively localized to mitochondria. Further, we establish that a CPM-modified rhodamine voltage reporter (RhoVR-CPM) shows improved localization to mitochondria in cells expressing mitochondrially-targeted esterases. Finally, RhoVR-CPM can be paired with fluorescence lifetime imaging microscopy (FLIM) to map changes in mitochondrial membrane potential.
{"title":"A chemical-genetic approach to target voltage-sensitive fluorophores to mitochondria","authors":"Julia G. Martin , Tong Zhan , Deshka L. Neill , Ke Xu , Evan W. Miller","doi":"10.1016/j.mitoco.2025.12.002","DOIUrl":"10.1016/j.mitoco.2025.12.002","url":null,"abstract":"<div><div>Mitochondria play central roles in the physiology of eukaryotic cells. Mitochondrial membrane potential, in turn, is a key driver of mitochondrial physiology. We previously developed a system to localize voltage-sensitive fluorophores to mitochondria based on the hydrolysis of labile acetoxymethyl (AM) esters. One potential problem with this system is the premature hydrolysis of the labile AM ester prior to accumulation in the mitochondria. A possible solution is to replace the AM ester with a bulky cyclopropylmethylacetoxy (CPM) ester, which resists uncatalyzed hydrolysis but can be removed by certain esterases. When paired with exogenous expression of mitochondrially-targeted esterases like porcine liver esterase (PLE), this chemical-genetic hybrid approach can improve localization to mitochondria. In this manuscript, we use superresolution microscopy to show that a variety of proteins, including esterases from pig and bacteria can be effectively localized to mitochondria. Further, we establish that a CPM-modified rhodamine voltage reporter (RhoVR-CPM) shows improved localization to mitochondria in cells expressing mitochondrially-targeted esterases. Finally, RhoVR-CPM can be paired with fluorescence lifetime imaging microscopy (FLIM) to map changes in mitochondrial membrane potential.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 109-115"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789904","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}
Mitochondrial Ca2+ plays important roles in shaping intracellular Ca2+ signaling and modulating energy metabolism. Dysregulated mitochondrial Ca2+ dynamics have been increasingly implicated in the pathogenesis of neurodegenerative disorders. To unravel how mitochondrial Ca2+ participates in the processes of neural activity and neurodegeneration, it is essential but challenging to monitor its dynamics in vivo. Recent advances in two-photon microscopy and genetically encoded Ca2+ indicators have enabled high-resolution imaging of mitochondrial Ca2+ in the brain. Here, we present a comprehensive protocol for in vivo imaging and analysis of mitochondrial Ca2+ 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 Ca2+ dynamics in vivo in both physiological and pathological contexts.
{"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}
Pub Date : 2025-01-01DOI: 10.1016/j.mitoco.2025.10.002
Hui Jiang
{"title":"PINK1-Parkin-mediated regulation of mitochondrial dynamics: A core function parallel to mitophagy control","authors":"Hui Jiang","doi":"10.1016/j.mitoco.2025.10.002","DOIUrl":"10.1016/j.mitoco.2025.10.002","url":null,"abstract":"","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 87-89"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519372","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}
Pub Date : 2024-01-01DOI: 10.1016/j.mitoco.2024.07.003
Xiaojie Wang , Qiyue Zhang , Suhong Xu
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 Caenorhabditis elegans 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 fzo-1: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 C. elegans and subsequent crossbreeding with the fzo-1: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.
{"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}
Pub Date : 2024-01-01DOI: 10.1016/j.mitoco.2024.10.001
Guoqiang Zhou , Zhenglong Gu , Jin Xu
Mitochondria play a pivotal role in cellular energetics, metabolism, and various regulatory processes. Their dysregulation is implicated in numerous diseases. Traditional population-level mitochondrial DNA (mtDNA) sequencing often obscures crucial information from individual cells, leading to a limited understanding of mitochondrial genetics. In contrast, single-cell mtDNA sequencing enables the precise detection and characterization of mtDNA mutations at the individual cell level, providing a nuanced view of mitochondrial heteroplasmy and its dynamics. This review aims to provide a comprehensive overview of current single-cell mtDNA sequencing methodologies and their applications in advancing our understanding of mitochondrial genetics.
{"title":"Single-cell mitochondrial DNA sequencing: Methodologies and applications","authors":"Guoqiang Zhou , Zhenglong Gu , Jin Xu","doi":"10.1016/j.mitoco.2024.10.001","DOIUrl":"10.1016/j.mitoco.2024.10.001","url":null,"abstract":"<div><div>Mitochondria play a pivotal role in cellular energetics, metabolism, and various regulatory processes. Their dysregulation is implicated in numerous diseases. Traditional population-level mitochondrial DNA (mtDNA) sequencing often obscures crucial information from individual cells, leading to a limited understanding of mitochondrial genetics. In contrast, single-cell mtDNA sequencing enables the precise detection and characterization of mtDNA mutations at the individual cell level, providing a nuanced view of mitochondrial heteroplasmy and its dynamics. This review aims to provide a comprehensive overview of current single-cell mtDNA sequencing methodologies and their applications in advancing our understanding of mitochondrial genetics.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 107-113"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571269","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}
Pub Date : 2024-01-01DOI: 10.1016/j.mitoco.2024.11.002
Qingzhu Chu , Wei-Ke Ji
Mitochondria are semiautonomous organelles that are actively shaped into an extended reticular network that is not connected to the endomembrane system via vesicular transport. Instead, active lipid exchange occurs between mitochondria and other organelles, such as the endoplasmic reticulum (ER) and lipid droplets (LDs), at mitochondrial membrane contact sites (MCSs), where the two organelles are juxtaposed with each other at a distance of 10–30 nm. Recent advances have led to an increasing understanding of the molecular mechanism that mediates the transfer of different lipid species between these organelles. Here, we highlight advances that demonstrate the role of lipid transfer proteins at ER–mitochondrial and LD–mitochondrial MCSs. Importantly, we summarize the fundamental questions on this topic that remain unanswered.
{"title":"Lipid transfer at mitochondrial membrane contact sites","authors":"Qingzhu Chu , Wei-Ke Ji","doi":"10.1016/j.mitoco.2024.11.002","DOIUrl":"10.1016/j.mitoco.2024.11.002","url":null,"abstract":"<div><div>Mitochondria are semiautonomous organelles that are actively shaped into an extended reticular network that is not connected to the endomembrane system via vesicular transport. Instead, active lipid exchange occurs between mitochondria and other organelles, such as the endoplasmic reticulum (ER) and lipid droplets (LDs), at mitochondrial membrane contact sites (MCSs), where the two organelles are juxtaposed with each other at a distance of 10–30 nm. Recent advances have led to an increasing understanding of the molecular mechanism that mediates the transfer of different lipid species between these organelles. Here, we highlight advances that demonstrate the role of lipid transfer proteins at ER–mitochondrial and LD–mitochondrial MCSs. Importantly, we summarize the fundamental questions on this topic that remain unanswered.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 123-128"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143975","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}
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