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}
{"title":"Off-target effects of mitochondrial oxidative phosphorylation inhibitors are common and can compromise the viability of cultured cells","authors":"Natalya Kozhukhar, Mikhail F. Alexeyev","doi":"10.1016/j.mitoco.2025.12.001","DOIUrl":"10.1016/j.mitoco.2025.12.001","url":null,"abstract":"<div><div>Mitochondrial respiratory chain inhibitors (MRCIs) are indispensable for studying cellular bioenergetics and its effects on various cellular processes. However, their off-target (those not mediated by respiratory chain inhibition) effects remain incompletely understood, even though their comprehension is crucial for the accurate interpretation of experimental outcomes. Here, we use four isogenic cell line pairs, which either have mitochondrial DNA (mtDNA) or lack it (ρ<sup>+</sup> or ρ<sup>0</sup> cells, respectively), to assess the possible off-target effects of widely used MRCIs antimycin A, oligomycin A, rotenone, and carbonyl cyanide m-chlorophenylhydrazone (CCCP). We examined clonogenic growth of ρ<sup>0</sup> cells and ρ<sup>+</sup> cells under conditions that either require the functional respiratory chain or do not. Unexpectedly, ρ<sup>0</sup> cells were sensitive to rotenone and antimycin A, even though these cells lack functional complex I and complex III, respectively, suggesting a nonspecific effect of these drugs. Furthermore, ρ<sup>0</sup> cells were more sensitive to CCCP than their ρ<sup>+</sup> counterparts. Intriguingly, the loss of the clonogenic potential in ρ<sup>+</sup> 143B cells could not be precisely correlated to the decrement of the mitochondrial inner membrane potential. These findings underscore the significance of off-target effects of MRCIs, which must be carefully considered when designing, conducting, and interpreting experiments involving these inhibitors.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 99-108"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683865","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}
Wenwen Xi , Zhiyan Zhang , Yi Su , Shuyi Wang , Yangzheng Ou , Bin Lu
{"title":"Frontiers in LONP1 research: Unraveling molecular mechanisms, disease associations, and therapeutic strategies","authors":"Wenwen Xi , Zhiyan Zhang , Yi Su , Shuyi Wang , Yangzheng Ou , Bin Lu","doi":"10.1016/j.mitoco.2025.10.001","DOIUrl":"10.1016/j.mitoco.2025.10.001","url":null,"abstract":"<div><div>LONP1 is a conserved mitochondrial AAA + protease central to mitochondrial proteostasis. This review summarizes its structural features, protease-chaperone functions, and roles in metabolic regulation (heme/sulfur/steroid pathways) and disease. In cancer, LONP1 overexpression drives tumor progression via metabolic reprogramming, EMT induction, metastasis, and therapy resistance, establishing it as a pan-cancer therapeutic target. Inhibitors face delivery and selectivity challenges, prompting future strategies like mitochondrial-targeted delivery and allosteric modulators. Research directions include mechanistic studies and clinical translation for cancer and neurodegenerative disorders.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"3 ","pages":"Pages 79-86"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415043","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":"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}
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}
Alessandro Maria Morelli , Ann Saada , Felix Scholkmann
{"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}
Julia G. Martin , Tong Zhan , Deshka L. Neill , Ke Xu , Evan W. Miller
{"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}
{"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}
{"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}
{"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}