Mitochondrion最新文献

{"title":"Targeting mitochondrial quality control for myocardial ischemia-reperfusion injury","authors":"Yuxuan He ,&nbsp;Sixu Ren ,&nbsp;Chenglin Liu ,&nbsp;Xiufen Zheng ,&nbsp;Cuilin Zhu","doi":"10.1016/j.mito.2025.102046","DOIUrl":"10.1016/j.mito.2025.102046","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) remains the leading global cause of mortality. Acute myocardial infarction (AMI) refers to acute myocardial ischemia resulting from thrombosis secondary to coronary atherosclerosis, which poses a major threat to human health. Clinically, timely revascularization (reperfusion) represents the basis of clinical treatment for AMI. However, secondary myocardial ischemia–reperfusion injury (MIRI) caused by reperfusion often exacerbates damage, representing a major challenge in clinical practice. Mitochondria represent essential organelles for maintaining cardiac function and cellular bioenergetics in MIRI. In recent years, the role of mitochondrial quality control (MQC) in maintaining cell homeostasis and mediating MIRI has been extensively studied. This review provides a concise overview of MQC mechanisms at the molecular, organelle, and cellular levels and their possible complex regulatory network in MIRI. In addition, potential treatment strategies targeting MQC to mitigate MIRI are summarized, highlighting the gap between current preclinical research and clinical transformation. Overall, this review provides theoretical guidance for further research and clinical translational studies.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102046"},"PeriodicalIF":3.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147788","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}

{"title":"Auditory neuropathy spectrum disorder and related auditory features in patients with hearing loss associated with the MT-TS1 m.7471dup variant","authors":"Shujiro Minami ,&nbsp;Amina Kida ,&nbsp;Satomi Inoue ,&nbsp;Haruka Murakami ,&nbsp;Noriko Morita ,&nbsp;Akira Takagi ,&nbsp;Takeshi Usui ,&nbsp;Tomoko Sugiuchi ,&nbsp;Kazuki Yamazawa ,&nbsp;Kiyomitsu Nara ,&nbsp;Hideki Mutai ,&nbsp;Tatsuo Matsunaga","doi":"10.1016/j.mito.2025.102056","DOIUrl":"10.1016/j.mito.2025.102056","url":null,"abstract":"<div><div>The m.7471dup variant of mitochondrial-tRNA Ser (UCN) (<em>MT-TS1</em>) is associated with sensorineural hearing loss (SNHL), neurological abnormalities, or both. Phenotypic variations in SNHL associated with the m.7471dup variant were the focus of our investigation. Five Japanese families carrying the variant were subjected to comprehensive genetic and clinical evaluations and audiometric testing. Notably, two families presented with auditory neuropathy spectrum disorder (ANSD), and two other families presented with auditory brainstem response thresholds much higher than those expected from the pure-tone audiometry results, which is analogous to ANSD. This is the first study to demonstrate that the m.7471dup variant can be associated with ANSD or similar characteristics. The penetrance of the m.7471dup variant was 71.4 % overall, with 100 % penetrance in cases with homoplasmy and 42.9 % penetrance in cases with heteroplasmy. Disease onset was congenital or early onset (≤ 6 years) in 80 % of the patients. The hearing levels ranged from normal to profound, and four subjects presented with neurological or psychiatric abnormalities. About 80 % of subjects who had newborn hearing screening passed the screening, suggesting late-onset or progressive hearing loss. These findings underscore the importance of rigorous follow-up evaluations, genetic counseling, and evaluation of educational environment considerations for patients carrying the m.7471dup variant.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102056"},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128152","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}

{"title":"Corrigendum to \"In vitro studies in VCP-associated multisystem proteinopathy suggest altered mitochondrial bioenergetics\" [Mitochondrion 22 (2015) 1-8].","authors":"Angèle Nalbandian, Katrina J Llewellyn, Arianna Gomez, Naomi Walker, Hailing Su, Andrew Dunnigan, Marilyn Chwa, Jouni Vesa, M C Kenney, Virginia E Kimonis","doi":"10.1016/j.mito.2025.102044","DOIUrl":"https://doi.org/10.1016/j.mito.2025.102044","url":null,"abstract":"","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":" ","pages":"102044"},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032731","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}

{"title":"Urolithin-A supplementation alleviates sepsis-induced acute lung injury by reducing mitochondrial dysfunction and modulating macrophage polarization","authors":"Mohd Mohsin ,&nbsp;Almaz Zaki ,&nbsp;Gulnaz Tabassum ,&nbsp;Salman Khan ,&nbsp;Shakir Ali ,&nbsp;Tanveer Ahmad ,&nbsp;Mansoor Ali Syed","doi":"10.1016/j.mito.2025.102047","DOIUrl":"10.1016/j.mito.2025.102047","url":null,"abstract":"<div><div>Sepsis is a severe and life-threatening condition marked by excessive inflammation, mitochondrial dysfunction, and epithelial barrier disruption, often leading to Acute Lung Injury (ALI). Mitophagy, a cellular mechanism that removes damaged mitochondria, plays a vital role in maintaining mitochondrial health during sepsis. In this study, we investigated the protective effects of Urolithin-A against ALI and sepsis. In LPS-stimulated RAW264.7 macrophages, Urolithin-A significantly reduced mitochondrial dysfunction, Reactive Oxygen Species (ROS), Nitric Oxide (NO) production, and apoptosis. Additionally, it enhanced mitophagy by upregulating PINK1, Parkin, and LC3-II, which helped preserve mitochondrial function.</div><div>In vivo, Urolithin-A treatment in mouse models of ALI and sepsis reduced lung injury and inflammation, as shown by improved ALI scores, decreased wet/dry lung weight ratios, and lower levels of inflammatory markers such as iNOS, IL-1β, and MPO. Urolithin-A also improved epithelial barrier integrity and upregulated anti-apoptotic markers, demonstrating its ability to alleviate sepsis-induced lung damage. These findings suggest that Urolithin-A holds significant promise as a therapeutic agent for managing inflammatory lung conditions associated with sepsis.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102047"},"PeriodicalIF":3.9,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928111","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}

{"title":"Exploring the microRNA-mitochondrial nexus in hepatocellular carcinoma","authors":"Ali Jawad Akki ,&nbsp;Srinivas Nanduri ,&nbsp;Shankargouda V Patil ,&nbsp;Kusal K Das ,&nbsp;Prachi Parvatikar","doi":"10.1016/j.mito.2025.102045","DOIUrl":"10.1016/j.mito.2025.102045","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are double-edged swords in hepatocellular carcinoma (HCC) that play a dual role in disease progression and suppression. The pivotal role of miRNAs in gene regulation emphasizes their potential to disrupt critical cellular processes, including mitochondrial function. Given the indispensable role of mitochondria in energy production, apoptosis, and metabolic control, all of which are central to HCC progression, understanding the miRNA-mitochondria axis is crucial. MiRNAs emerge as pivotal regulators of mitochondrial function, exerting profound influence over HCC progression. This comprehensive review delves into the multifaceted roles of miRNAs in modulating mitochondrial biogenesis, dynamics, and apoptosis. MiRNA impacts key metabolic pathways, including energy metabolism, fatty acid metabolism, and oxidative stress. The intricate interplay between miRNAs and mitochondrial function extends to the regulation of mitophagy and ferroptosis. By exploring the microRNA-mitochondrial axis, this review offers insights for identifying novel diagnostic and therapeutic targets.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102045"},"PeriodicalIF":3.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874550","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}

{"title":"Mitochondrial transplantation: Triumphs, challenges, and impacts on nuclear genome remodelling","authors":"Elly H. Shin ,&nbsp;Quinn Le ,&nbsp;Rachel Barboza ,&nbsp;Amanda Morin ,&nbsp;Shiva M. Singh ,&nbsp;Christina A. Castellani","doi":"10.1016/j.mito.2025.102042","DOIUrl":"10.1016/j.mito.2025.102042","url":null,"abstract":"<div><div>Mitochondria are membrane-bound organelles of eukaryotic cells that play crucial roles in cell functioning and homeostasis, including ATP generation for cellular energy. Mitochondrial function is associated with several complex diseases and disorders, including cardiovascular, cardiometabolic, neurodegenerative diseases and some cancers. The risk for these diseases and disorders is often associated with mitochondrial dysfunction, particularly the quantitative and qualitative features of the mitochondrial genome. Emerging results implicate mito-nuclear crosstalk as the mechanism by which mtDNA variation affects complex disease outcomes. Experimental approaches are emerging for the targeting of mitochondria as a potential therapeutic for several of these diseases, particularly in the form of mitochondrial transplantation. Current approaches to mitochondrial transplantation generally involve isolating healthy mitochondria from donor cells and introducing them to diseased recipients towards amelioration of mitochondrial dysfunction. Using such a protocol, several reports have shown recovery of mitochondrial function and improved disease outcomes post-mitochondrial transplantation, highlighting its potential as a therapeutic method for several complex, severe and debilitating diseases. Additionally, the mitochondrial genome can be modified prior to transplantation to target disease-associated site-specific mutations and to reduce the ratio of mutant-to-WT alleles. These promising results may underlie the potential impact of mitochondrial transplantation on mito-nuclear genome interactions in the setting of the disease. Further, we recommend that mitochondrial transplantation experimentation include an assessment of potential impacts on remodelling of the nuclear genome, particularly the nuclear epigenome and transcriptome. Herein, we review these and other triumphs and challenges of mitochondrial transplantation as a potential novel therapeutic for mitochondria-associated diseases.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102042"},"PeriodicalIF":3.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874549","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}

{"title":"Cell-specific mitochondrial response in progressive supranuclear palsy","authors":"Valerie Sackmann ,&nbsp;Nasna Nassir ,&nbsp;Satoshi Tanikawa ,&nbsp;Shelley L. Forrest ,&nbsp;Helen Chasiotis ,&nbsp;Jun Li ,&nbsp;Shehzad Hanif ,&nbsp;Ivan Martinez-Valbuena ,&nbsp;Maria Carmela Tartaglia ,&nbsp;Anthony E. Lang ,&nbsp;Mohammed Uddin ,&nbsp;Alexei Verkhratsky ,&nbsp;Gabor G. Kovacs","doi":"10.1016/j.mito.2025.102043","DOIUrl":"10.1016/j.mito.2025.102043","url":null,"abstract":"<div><div>Progressive supranuclear palsy (PSP) is a main form of idiopathic tauopathy characterized neuropathologically by subcortical neurofibrillary tangles in neurons, oligodendroglial coiled bodies, and tufted astrocytes, which follow sequential distribution in the human brain. Mitochondrial dysfunction is thought to be a contributor to many neurodegenerative diseases, but its role in PSP at the cellular level remains incompletely understood. To address this, we performed cell-specific morphometric analysis of mitochondrial markers in post-mortem tissues from motor cortex of PSP patients and non-diseased controls (n = 5 each) followed by single-nuclear transcriptomics (n = 3 each) to identify changes in genes that regulate mitochondrial function. We treated iCell astrocytes with PSP brain homogenates and isolated viable astrocytes from multiple regions of PSP-affected brains. We found that PSP is characterized by significant mitochondrial changes in neurons and astrocytes at the immunohistochemical level, particularly in complex I, with distinct transcriptomic responses across cell types. Glial cells exhibited upregulation of pathways associated with mitochondrial function. In contrast, excitatory and inhibitory neurons showed downregulation in these pathways, indicating impaired mitochondrial function. Astrocytes derived from different human brain regions express varied levels of GFAP and EAAT1 immunoreactivity. Astrocytic tau pathology in cell culture derived from postmortem PSP brains mirrors that seen in corresponding brain tissue histology. Tau pathology in human astrocyte cell culture is associated with clumps of mitochondria potentially associated with impairment in their neuron supportive function. Our results underscore selective complex I damage and cell-type specific patterns that differentiate PSP from other neurodegenerative diseases.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102043"},"PeriodicalIF":3.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882467","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}

{"title":"Mitochondrial quality control and stress signaling pathways in the pathophysiology of cardio-renal diseases","authors":"Isabel Amador-Martínez ,&nbsp;Ana Karina Aranda-Rivera ,&nbsp;Mauricio Raziel Martínez-Castañeda ,&nbsp;José Pedraza-Chaverri","doi":"10.1016/j.mito.2025.102040","DOIUrl":"10.1016/j.mito.2025.102040","url":null,"abstract":"<div><div>Mitochondria are essential organelles for cellular function and have become a broad field of study. In cardio-renal diseases, it has been established that mitochondrial dysfunction is a primary mechanism leading to these pathologies. Under stress, mitochondria can develop stress response mechanisms to maintain mitochondrial quality control (MQC) and functions. In contrast, the perturbation of these mechanisms has been associated with the pathogenesis of several diseases. Thus, targeting specific pathways within MQC could offer a therapeutic avenue for protecting mitochondrial integrity. However, the mechanisms related to MQC and mitochondrial stress signaling in the cardio-renal axis have been poorly explored. The primary limitations include the lack of reproducibility in the experimental models of cardio-renal disease, the incomplete knowledge of molecules that generate bidirectional damage, and the temporality of the study models. Therefore, we believe that integration of all of those limitations, along with recent advances in MQC mechanisms (i.e., mitophagy), stress signaling pathways (e.g., integrated stress response, mitochondrial unfolded protein response, and mitochondrial protein import), associated pharmacology, and targeted therapeutic approaches could reveal what the deregulation of these mechanisms is like and provide ideas for generating strategies that seek to avoid the progression of cardio-renal diseases.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102040"},"PeriodicalIF":3.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850285","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}

{"title":"MiR-718-mediated inhibition of prohibitin 1 influences mitochondrial dynamics, proliferation, and migration of keratinocytes","authors":"Himani Rani ,&nbsp;Neeru Saini","doi":"10.1016/j.mito.2025.102041","DOIUrl":"10.1016/j.mito.2025.102041","url":null,"abstract":"<div><div>Keratinocyte hyperproliferation is a key characteristic of psoriasis. Prohibitins (PHB) are known to be associated with keratinocyte proliferation and cell cycle regulation, influenced by mitochondrial processes. The objective of this study was to examine the impact of miR-718 overexpression and downregulation on the various PHB1-mitochondria-driven activities in HaCaT keratinocytes. We demonstrated that PHB1 expression is downregulated through direct targeting by miR-718, which then leads to a reduction in the expression of MFN1, MFN2, and OPA1 in miR-718-transfected cells, as evidenced by western blot analysis. Mitochondrial fusion and DRP1-mediated fission, as indicated by western blot results, were further validated using confocal imaging with CMXRoS labeling, contrasting with the effects of AM-718. JC-1 dye staining results demonstrated the miR-718 overexpression facilitates the mitochondrial membrane depolarization that highlighting the PHB1-OPA1 mediated depolarization. Moreover, OPA1 maintains mitochondrial cristae structure and its dysfunction can trigger cell death. Further PHB1 is known to regulate OPA1 function, alters mitochondrial morphology and significantly influences epithelial cell migration. Herein, our data demonstrated a reduction in keratinocyte proliferation and migration, as evidenced by the CCK assay and wound healing assay, respectively, following 24 h of transfection. Ultimately, our data indicates the potential involvement of miR-718 in the mitochondria-mediated suppression of cell proliferation and migration in HaCaT keratinocytes, likely due to modified mitochondrial processes via PHB1.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102041"},"PeriodicalIF":3.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850284","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}

{"title":"Miro1- a key player in β-cell function and mitochondrial dynamics under diabetes mellitus","authors":"Srikanth Kavyashree,&nbsp;Kannan Harithpriya,&nbsp;Kunka Mohanram Ramkumar","doi":"10.1016/j.mito.2025.102039","DOIUrl":"10.1016/j.mito.2025.102039","url":null,"abstract":"<div><div>Mitochondrial health is crucial for the survival and function of β-cells, preserving glucose homeostasis and effective insulin production. Miro1, a mitochondrial Rho GTPase1 protein, plays an essential role in maintaining the<!--> <!-->quality of mitochondria by regulating calcium homeostasis and mitophagy. In this review, we aim to explore the dysfunction of Miro1 in type 2 diabetes mellitus (T2DM) and its contribution to impaired Ca²⁺ signaling, which increases oxidative stress in β-cells. This dysfunction is the hallmark of T2DM pathogenesis, leading to insufficient insulin production and poor glycemic control. Additionally, we discuss the role of Miro1 in modulating insulin secretion and inflammation, highlighting its effect on modulating key signaling cascades in β-cells. Altogether, enhancing Miro1 function and activity could alleviate mitochondrial dysfunction, reducing oxidative stress-mediated damage, and improving pancreatic β-cell survival. Targeting Miro1 with small molecules or gene-editing approaches could provide effective strategies for restoring cell function and insulin secretion in diabetic individuals. Exploring the deeper knowledge of Miro1 functions and interactions could lead to novel therapeutic advances in T2DM management.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102039"},"PeriodicalIF":3.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825893","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}