Mitochondrion最新文献

Unmasking NLRX1: Exploring the broadening biological landscape of a mysterious mitochondrial sensor 揭开NLRX1的面纱：探索一种神秘的线粒体传感器的生物景观。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-05-01 Epub Date: 2026-02-10 DOI: 10.1016/j.mito.2026.102133

Jagabandhu Bag , Sabyasachi Banerjee , Subhasis Banerjee , SK Ashok Kumar , Sourav De

{"title":"Unmasking NLRX1: Exploring the broadening biological landscape of a mysterious mitochondrial sensor","authors":"Jagabandhu Bag , Sabyasachi Banerjee , Subhasis Banerjee , SK Ashok Kumar , Sourav De","doi":"10.1016/j.mito.2026.102133","DOIUrl":"10.1016/j.mito.2026.102133","url":null,"abstract":"<div><div>The nucleotide-binding oligomerization domain-like receptor (NLR) family is an important family of cytoplasmic pathogen recognition receptors involved in innate immune defense. Among them, NLR family member X1 (NLRX1) stands out with its specific N-terminal targeting sequence that targets it to mitochondria and thereby couples immune regulation with mitochondrial function. Recent findings point to NLRX1 as an important negative regulator of inflammation and also a modulator of mitochondrial metabolism and autophagy. Recent research has amplified our knowledge of the multifunctional biological functions of NLRX1, which involve it in the pathogenesis and development of several inflammatory, autoimmune, metabolic, and cancerous disorders. Despite significant progress, the specific molecular mechanisms involved in NLRX1-regulated cellular homeostasis are still not fully elucidated. In this review, we compile and critically review the recent data on NLRX1, highlighting its molecular interactions, signaling pathways, and disease-modulating functional relevance. Integrating findings from recent experimental and clinical research, this review attempts to discern the general biological significance of NLRX1 as well as its promise as an emerging therapeutic target in the new era of advanced research.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"88 ","pages":"Article 102133"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181065","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}

引用次数: 0

Short telomeres in mitochondrial DNA depletion disorders 线粒体DNA耗竭症中的短端粒。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-05-01 Epub Date: 2026-02-10 DOI: 10.1016/j.mito.2026.102131

Yumi Dille , Emmanouil Rampakakis , Geraldine Aubert , Christelle Dassi , William Mannherz , Saoussen Berrahmoune , Myriam Srour , Daniela Buhas , Suneet Agarwal , Kenneth A. Myers

引用次数: 0

Mitochondrial dysfunction–induced PANoptosis: Mechanisms, triggers, and disease implications 线粒体功能障碍诱导的PANoptosis：机制、触发因素和疾病含义。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-05-01 Epub Date: 2026-01-25 DOI: 10.1016/j.mito.2026.102115

Liyang Pan , Shijie Fang , Fanhua Kong , Shaojun Ye , Yan Xiong

{"title":"Mitochondrial dysfunction–induced PANoptosis: Mechanisms, triggers, and disease implications","authors":"Liyang Pan , Shijie Fang , Fanhua Kong , Shaojun Ye , Yan Xiong","doi":"10.1016/j.mito.2026.102115","DOIUrl":"10.1016/j.mito.2026.102115","url":null,"abstract":"<div><div>In recent years, PANoptosis, as a novel form of cell death that integrates multiple cell death pathways, has progressively emerged as a cutting-edge research field in the study of cell death and immune regulation. PANoptosis, a recently proposed form of inflammatory programmed cell death, integrates features of pyroptosis, apoptosis, and necroptosis, while emphasizing their interplay. It is mediated by the PANoptosome and plays a pivotal role in infections, inflammation, tumors, and degenerative diseases. Recent studies have demonstrated that ROS serve as critical signaling molecules for PANoptosome assembly. Given that mitochondria constitute the primary intracellular source of ROS, this establishes a crucial link between mitochondrial and PANoptosis activation. Mitochondria sustain energy production, calcium homeostasis, and signaling but also contribute to immune responses and cell death. Oxidative stress, obesity, and environmental pollutants can induce mitochondrial dysfunction, manifested through impaired mitochondrial dynamics, which subsequently leads to excessive ROS production and mtDNA leakage. These pathological changes ultimately trigger PANoptosis activation. This review systematically summarizes how mitochondrial dysfunction triggers PANoptosis through mechanisms such as ROS accumulation, aberrant mitochondrial dynamics, and mtDNA leakage. Furthermore, it explores the implications of this process in traumatic brain injury, inflammatory diseases, ischemic disorders, and diseases induced by environmental toxins (e.g., microplastics and heavy metals). Understanding the interplay between mitochondria and PANoptosis may provide critical insights into the pathogenesis of inflammation-related diseases and offer novel mitochondria-targeted therapeutic strategies.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"88 ","pages":"Article 102115"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064921","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}

引用次数: 0

PP2A inhibition alleviates DCD liver damage during prolonged cold ischemia by interfering Drp1 translocation and ER stress PP2A抑制通过干扰Drp1易位和内质网应激，减轻长时间冷缺血时DCD肝损伤。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-05-01 Epub Date: 2026-01-24 DOI: 10.1016/j.mito.2026.102118

Jianan Lan , Zhongshan Lu , Quanwei Cheng , Yujie Sun , Shaojun Ye , Yan Xiong

{"title":"PP2A inhibition alleviates DCD liver damage during prolonged cold ischemia by interfering Drp1 translocation and ER stress","authors":"Jianan Lan , Zhongshan Lu , Quanwei Cheng , Yujie Sun , Shaojun Ye , Yan Xiong","doi":"10.1016/j.mito.2026.102118","DOIUrl":"10.1016/j.mito.2026.102118","url":null,"abstract":"<div><div>Prolonged cold ischemia-warm reperfusion (PCI/WR) of donor livers is an independent risk factor for primary nonfunction (PNF) after liver transplantation (LT). Previous studies have demonstrated that may be related to hepatocyte apoptosis mediated by the abnormal mitochondrial division. In the present study, we report that PCI/WR up-regulated apoptotic signals in donation after circulatory death (DCD) rat livers after 24 h of cold ischemia, increased the expression of PP2A, Drp1 and CHOP, and led to caspase-induced apoptosis. Downregulation of PP2A attenuated PCI/WR-induced hepatocyte injury, improved liver function, and decreased the expression of Drp1 and CHOP. In particular, okadaic acid (OA) inhibited the translocation of Drp1 to mitochondria and the release of Cyt c into the cytoplasm. Further investigation found that inhibiting mitochondrial division or ER-stress could slightly reverse the apoptosis rate induced by PCI/WR, while not affecting PP2A expression in vivo or <em>in vitro</em>. These observations indicated that PP2A involved in the regulation of hepatocyte apoptosis after prolonged cold storage, possibly through inhibiting the expression of Drp1 and CHOP, as well as Drp1 translocation. Our results provide evidence that PP2A could be a potential target for therapeutic intervention of DCD livers subjected to prolonged cold ischemia.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"88 ","pages":"Article 102118"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053067","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}

引用次数: 0

Transcriptional activation by MNRR1 is effected by recruiting p300 and can be induced by minimal peptides MNRR1的转录激活是通过募集p300来实现的，并且可以通过最少的肽来诱导。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-05-01 Epub Date: 2026-01-25 DOI: 10.1016/j.mito.2026.102119

Neeraja Purandare , Vignesh Pasupathi , Deepesh Padhan , Sagarika Rai , Lawrence I. Grossman , Siddhesh Aras

{"title":"Transcriptional activation by MNRR1 is effected by recruiting p300 and can be induced by minimal peptides","authors":"Neeraja Purandare , Vignesh Pasupathi , Deepesh Padhan , Sagarika Rai , Lawrence I. Grossman , Siddhesh Aras","doi":"10.1016/j.mito.2026.102119","DOIUrl":"10.1016/j.mito.2026.102119","url":null,"abstract":"<div><div>Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1; also, CHCHD2, PARK22, AAG10), which functions in both the mitochondria and the nucleus, modulates mitochondrial function as well as cellular stress response. We have previously shown that stress response is predominantly mediated by its nuclear function as a transcriptional regulator at an 8-bp DNA element. This 8-bp element is the consensus DNA binding site for the transcription factor Recombination Signal Binding Protein For Immunoglobulin Kappa J Region (RBPJk). Here we have refined the mechanism by which MNRR1 regulates transcription at the ORE. We show that MNRR1 interacts with RBPJk and recruits the transcriptional co-activator p300 to facilitate transcription. We also show that a minimal domain of MNRR1 is sufficient to activate its nuclear function. Peptides based on this minimal domain can activate transcription by MNRR1 by enhancing p300 and RBPJk interaction. MNRR1 peptides activate downstream pathways such as mitochondrial biogenesis and the unfolded protein response (UPRmt) in an in vitro model for MELAS.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"88 ","pages":"Article 102119"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063957","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}

引用次数: 0

Probability of Mitochondrial DNA heteroplasmy in different tissues from European populations 欧洲人群不同组织线粒体DNA异质性的可能性

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-05-01 Epub Date: 2026-01-31 DOI: 10.1016/j.mito.2026.102117

Daniel R. Cuesta-Aguirre, Ana Onieva, M. Pilar Aluja, Cristina Santos

引用次数: 0

Mitochondrial iron overload is associated with lysosomal dysfunction-mediated mitophagy impairment in the heart of Friedreich’s ataxia 线粒体铁超载与弗里德赖希共济失调心脏溶酶体功能障碍介导的线粒体自噬损伤有关。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-05-01 Epub Date: 2026-01-31 DOI: 10.1016/j.mito.2026.102120

Eunbin Jee , Maisha Medha , Hwayoung Baek , Jonghan Kim , Yuho Kim

{"title":"Mitochondrial iron overload is associated with lysosomal dysfunction-mediated mitophagy impairment in the heart of Friedreich’s ataxia","authors":"Eunbin Jee , Maisha Medha , Hwayoung Baek , Jonghan Kim , Yuho Kim","doi":"10.1016/j.mito.2026.102120","DOIUrl":"10.1016/j.mito.2026.102120","url":null,"abstract":"<div><div>Friedreich’s ataxia (FRDA) is a rare disease caused by deficiency of frataxin, a mitochondrial protein essential for iron-sulfur cluster assembly and iron homeostasis. In addition to neurological symptoms, cardiac dysfunction is common and represents a major cause of premature death in FRDA. Although iron overload has been suggested as a major player for FRDA-related cardiomyopathy, its underlying mechanisms remain unclear. Using heart-specific frataxin deficient mice, we observed that FRDA-related cardiac hypertrophy is accompanied by mitochondrial iron overload. Transmission electron microscopy (TEM) revealed iron aggregates within cardiac mitochondria, whose ultrastructure was severely altered. Along with the iron deposits and structural abnormalities, mitochondrial respiration was markedly impaired in FRDA hearts, despite the absence of increased oxidative stress. Notably, although dysfunctional mitochondria accumulate in parallel with enhanced mitochondrial biogenesis, the clearance of damaged or dysfunctional mitochondria (i.e., mitophagy) is disrupted, as evidenced by excessive accumulation of p62 and Parkin proteins. The lysosomal system, which plays a central role for mitochondrial turnover, appears to be dysregulated via the mTOR-TFEB axis. Hyperactivation mTOR inhibits lysosomal biogenesis and function, although lysosomal content remains unchanged. Collectively, our study provides mechanistic insight into the role of mitochondrial iron aggregates in the pathogenesis of FRDA-related cardiomyopathy and suggests a potential contribution of lysosomal dysfunction to impaired mitochondrial quality control in the context of cardiac frataxin deficiency.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"88 ","pages":"Article 102120"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106324","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}

引用次数: 0

A 3-hit metabolic signaling model for the core symptoms of autism spectrum disorder 自闭症谱系障碍核心症状的3击代谢信号模型

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-03-01 Epub Date: 2025-11-14 DOI: 10.1016/j.mito.2025.102096

Robert K. Naviaux

{"title":"A 3-hit metabolic signaling model for the core symptoms of autism spectrum disorder","authors":"Robert K. Naviaux","doi":"10.1016/j.mito.2025.102096","DOIUrl":"10.1016/j.mito.2025.102096","url":null,"abstract":"<div><div>A 3-hit metabolic signaling model of the causes of autism spectrum disorder (ASD) is described. The 3-hits required for ASD are: 1) inheritance of a genotype that sensitizes mitochondria and/or eATP-stimulated, intracellular calcium signaling to environmental change, 2) early exposure to environmental triggers that activate the metabolic features of the cell danger response (CDR), and 3) recurrent or persistent exposure to CDR-activating triggers for at least 3–6 months during the critical neurodevelopmental window from the late 1st trimester of pregnancy to the first 18–36 months of life. The three hits associated with an increased risk of ASD can be functionally classified as primers, triggers, and amplifiers of the CDR, respectively. Since the CDR is maintained by metabolic signaling, this new model creates a unified intellectual framework for understanding how the diverse features of ASD are connected. The example of phenylketonuria (PKU) is given to show that even disorders with very strong genetic predispositions can follow this 3-hit developmental paradigm and still be treatable using the principles of metabolic signaling. Since the 2nd and 3rd hits are modifiable, this model predicts that if the children at greatest risk can be diagnosed and treated before symptoms occur, some of these children may never develop ASD, and if diagnosed after symptoms occur, the core symptoms that are most disabling can be decreased significantly.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"87 ","pages":"Article 102096"},"PeriodicalIF":4.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534640","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}

引用次数: 0

Mitochondrial responses to thermal stress: ROS dynamics and metabolic shifts in Drosophila 线粒体对热应激的反应：果蝇的ROS动力学和代谢变化。

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-03-01 Epub Date: 2026-01-25 DOI: 10.1016/j.mito.2026.102114

Adèle Léger , Léa Herpe , Nicolas Pichaud

{"title":"Mitochondrial responses to thermal stress: ROS dynamics and metabolic shifts in Drosophila","authors":"Adèle Léger , Léa Herpe , Nicolas Pichaud","doi":"10.1016/j.mito.2026.102114","DOIUrl":"10.1016/j.mito.2026.102114","url":null,"abstract":"<div><div>Temperature critically impacts ectotherm metabolism, notably mitochondrial respiration, enzyme activity, and ATP production. However, the effect of temperature on reactive oxygen species (ROS) production remains poorly understood in these organisms. Here, we investigated the thermal sensitivity of H<sub>2</sub>O<sub>2</sub> production by isolated mitochondria from <em>Drosophila melanogaster</em>. We measured H<sub>2</sub>O<sub>2</sub> emission rates at six temperatures (18–45 °C) during: (i) oxidative phosphorylation (OXPHOS) fueled by NADH-linked substrates feeding electrons into complex I (CI), as well as by FADH<sub>2</sub>-linked substrates such as proline, succinate, and glycerol-3-phosphate (G3P); and (ii) during non-phosphorylating conditions with FADH<sub>2</sub>-linked substrates as well as using defined substrate/inhibitor combinations such as pyruvate, malate and rotenone (P/M−driven), as well as supported by proline, succinate, and G3P when inhibitors are present. We calculated relative H<sub>2</sub>O<sub>2</sub> emission rates and compared them with previously measured enzyme activities and oxygen consumption rates. Our results show marked thermal sensitivity of H<sub>2</sub>O<sub>2</sub> emission during OXPHOS and when P/M−driven. At elevated temperatures, increased ROS production by NADH-linked substrates during OXPHOS coincided with a decline in CI-induced oxygen consumption capacity and pyruvate dehydrogenase (PDH) activity, indicating a dysfunction in NADH-producing and -consuming systems. In contrast, substrates feeding electrons into the Q pool via FADH<sub>2</sub> oxidation support respiration at high temperature decoupled from ROS production, suggesting a metabolic strategy to sustain respiration while limiting oxidative stress. These findings highlight that mitochondrial thermal sensitivity involves a complex regulation of ROS metabolism. Our study provides new insights into mitochondrial ROS dynamics and their implications for upper thermal tolerance in insects.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"87 ","pages":"Article 102114"},"PeriodicalIF":4.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064893","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}

引用次数: 0

Exogenous mitochondrial transfer alleviates neurodegeneration in Parkinson’s disease model by improving mitochondrial function 外源性线粒体转移通过改善线粒体功能减轻帕金森病模型神经退行性变

IF 4.5 3区生物学

Mitochondrion Pub Date : 2026-03-01 Epub Date: 2026-01-26 DOI: 10.1016/j.mito.2026.102111

Yu Si , Muhammad Abid Hayat , Yingyin Ni , Jingwen Zhang , Tao Guo , Yudie Cao , Yancheng Hong , Hao Zuo , Xin Sun , Zheng Li , Bo Chen , Jia Wan , Yong Wang , Jiabo Hu

{"title":"Exogenous mitochondrial transfer alleviates neurodegeneration in Parkinson’s disease model by improving mitochondrial function","authors":"Yu Si , Muhammad Abid Hayat , Yingyin Ni , Jingwen Zhang , Tao Guo , Yudie Cao , Yancheng Hong , Hao Zuo , Xin Sun , Zheng Li , Bo Chen , Jia Wan , Yong Wang , Jiabo Hu","doi":"10.1016/j.mito.2026.102111","DOIUrl":"10.1016/j.mito.2026.102111","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is the second most common neurodegenerative disorder related to mitochondrial dysfunction. Recent studies have reported that mitochondrial transfer between cells occurred naturally and was effective for alleviating mitochondrial dysfunction. In the current study, functional exogenous mitochondria (Mito) were extracted and administered to both in vitro and in vivo PD models, exploring the therapeutic effects of Mito on damaged neurons. It was observed that in the in vitro PD model, Mito improved cell morphology and increased cell viability from 25.06% to 42.44% (p < 0.001), while enhancing mitochondrial activity within the cells by a 201% increase in the JC-1 red/green fluorescence ratio (p = 0.02). Further analysis suggests that Mito’s neuroprotective effects are potentially mediated via integrated modulation of neuroinflammation and ferroptosis pathways. The findings of the in vivo PD model showed that Mito improved motor coordination in the rotational test by 71% (p < 0.01) and ameliorated depression-like behavior demonstrating a 13.4% enhancement in Sucrose preference (p < 0.001), accompanied by histological evidence of neuroprotection observed in Nissl-stained brain sections and the significant recovery in mitochondrial function by 31.6% (p = 0.01). This study is the first to demonstrate that Mito can enter a PD cell model and rescue neuronal and mitochondrial damage in both in vivo and in vitro settings, with transcriptomic analysis revealing the involvement of key molecular pathways related to neuroinflammation and ferroptosis. This offers new insights and prospectus therapeutic strategies for PD as well as a foundation for future research in clinical medicine.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"87 ","pages":"Article 102111"},"PeriodicalIF":4.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078070","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}

引用次数: 0