Mitochondrion最新文献

{"title":"Loss of PGC-1α causes depot-specific alterations in mitochondrial capacity, ROS handling and adaptive responses to metabolic stress in white adipose tissue","authors":"Anders Gudiksen,&nbsp;Eva Zhou,&nbsp;Louise Pedersen,&nbsp;Catherine A. Zaia,&nbsp;Cecilie E. Wille,&nbsp;Elisabeth V. Eliesen,&nbsp;Henriette Pilegaard","doi":"10.1016/j.mito.2025.102034","DOIUrl":"10.1016/j.mito.2025.102034","url":null,"abstract":"<div><div>White adipose tissue (WAT) delivers lipid-fueled metabolic support to systemic energy expenditure through control of lipolytic and re-esterifying regulatory pathways, facilitated by mitochondrial bioenergetic support. Mitochondria are important sources of reactive oxygen species (ROS) and oxidative damage may potentially derail adipocyte function when mitochondrial homeostasis is challenged by overproduction of ROS. Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α is a transcriptional co-activator that in skeletal muscle plays a central role in mitochondrial biogenesis and function but whether PGC-1α is equally important for mitochondrial function and adaptations in white adipose tissue remains to be fully resolved. The aim of the present study was to characterize the necessity of adipocyte PGC-1α for adaptive regulation of mitochondrial function in distinct white adipose depots. PGC-1α adipose tissue-specific knockout (ATKO) and floxed littermate control mice (CTRL) were subjected to either 24 h of fasting or 48 h of cold exposure. Bioenergetics, ROS handling, basal and adaptive protein responses, markers of protein damage as well as lipid cycling capacity and regulation were characterized in distinct WAT depots.</div><div>ATKO mice demonstrated impairments in respiration as well as reduced OXPHOS protein content in fed and fasted conditions. Increased ROS emission in tandem with diminished mitochondrial antioxidant defense capacity resulted in increased protein oxidation in ATKO WAT. Adipose tissue PGC-1α knockout also led to changes in regulation of lipolysis and potentially triglyceride reesterification in WAT. In conclusion, PGC-1α regulates adipose tissue mitochondrial respiration and ROS balance as well as lipid cycling during metabolic challenges in a depot specific manner.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102034"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beneficial effects of mitophagy enhancers on amyloid beta-induced mitochondrial and synaptic toxicities in Alzheimer’s disease","authors":"Sudhir Kshirsagar ,&nbsp;Arubala P. Reddy ,&nbsp;P.Hemachandra Reddy","doi":"10.1016/j.mito.2025.102038","DOIUrl":"10.1016/j.mito.2025.102038","url":null,"abstract":"<div><div>The purpose of our study is to investigate the beneficial effects of mitophagy enhancers against mutant amyloid precursor protein (APP) and amyloid beta (Aβ) induced mitochondrial and synaptic toxicities in Alzheimer’s disease (AD). Research spanning over two decades highlights the critical role of mitochondrial dysfunction and synaptic damage in the pathogenesis of both early-onset and late-onset AD. Emerging evidence suggests impaired clearance of damaged mitochondria is an early pathological event in AD, positioning mitophagy enhancers as potential therapeutic candidates. This study determined the optimal doses of four mitophagy enhancers—Urolithin A (UA), actinonin, tomatidine, and nicotinamide riboside (NR)—using immortalized mouse hippocampal (HT22) neurons. HT22 cells were transfected with mutant APP (mAPP) cDNA and treated with the enhancers. The effects were assessed by evaluating mRNA and protein expression levels of genes involved in mitochondrial dynamics, biogenesis, mitophagy, and synaptic function, alongside cell survival and mitochondrial respiration. Mitochondrial morphology was also examined in treated and untreated mAPP-HT22 cells. Results showed that mAPP-HT22 cells exhibited increased mitochondrial fission, reduced fusion, downregulated synaptic and mitophagy-related genes, diminished cell survival, impaired mitochondrial respiration, and excessively fragmented, shortened mitochondria. Treatment with mitophagy enhancers reversed these deficits, restoring mitochondrial and synaptic health. Enhanced cell survival, upregulation of mitochondrial fusion, synaptic, and mitophagy genes, improved mitochondrial structure, and reduced fragmentation were observed. Notably, UA demonstrated the most robust mitigating effects. These findings underscore the therapeutic potential of mitophagy enhancers, particularly UA, as promising candidates to treat mitochondrial and synaptic dysfunctions in AD.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102038"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738235","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 DNA copy number and Alzheimer’s disease and Parkinson disease","authors":"Pei Qin ,&nbsp;Xiaojuan Chen ,&nbsp;Panpan Ma ,&nbsp;Xinying Li ,&nbsp;Yunying Lin ,&nbsp;Xiaoning Liu ,&nbsp;Xiaoyan Liang ,&nbsp;Tianhang Qin ,&nbsp;Junyan Liang ,&nbsp;Jipeng Ouyang","doi":"10.1016/j.mito.2025.102032","DOIUrl":"10.1016/j.mito.2025.102032","url":null,"abstract":"<div><h3>Introduction</h3><div>A systematic review on the association of mitochondrial DNA copy number (mtDNA-CN) with Alzheimer’s disease (AD) and Parkinson disease (PD) is lacking and the causal relationship remains unclear.</div></div><div><h3>Objective</h3><div>We aimed to conduct a systematic review of observational studies on the association of mtDNA-CN with AD and PD and perform a bidirectional 2-sample Mendelian randomization (MR) study to investigate their causal relationships.</div></div><div><h3>Methods</h3><div>PubMed, Embase, and Web of Science were searched for eligible studies before Jan 2025. The causal links were conducted with inverse-variance weighted (IVW) method as the main analysis.</div></div><div><h3>Results</h3><div>Fourteen case-control and 2 cohort studies investigated the association between mtDNA-CN and AD, with 13 reporting decreased mtDNA-CN associated with increased risk of AD and 3 showing no significant association. All the studies (9 case-control, 1 cross-sectional, 2 cohort studies) observed the relation between mtDNA-CN and PD except for 3 studies reporting no significant association. In MR analysis, genetically predicted mtDNA-CN was not associated with AD and PD, whereas genetically predicted AD (β −0.085, 95 % CI −0.156 to −0.013; <em>P</em> = 0.02) but not PD was associated with mtDNA-CN. Sensitivity and replication analyses showed a stable finding.</div></div><div><h3>Discussion</h3><div>The systematic review found limited observational studies on mtDNA-CN and AD and PD and majority were case-control study. Findings of the bidirectional MR study did not support a causal effect of mtDNA-CN in the development of AD and PD but found that AD can lead to decreased levels of mtDNA-CN, which suggest mtDNA-CN as a potential biomarker of AD.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102032"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738246","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":"Drp1 knockdown aggravates obesity-induced cardiac dysfunction and remodeling","authors":"Dan Wu ,&nbsp;Qingxun Hu ,&nbsp;Huimin Li ,&nbsp;Yun Yin ,&nbsp;Pei Wang ,&nbsp;Wang Wang","doi":"10.1016/j.mito.2025.102023","DOIUrl":"10.1016/j.mito.2025.102023","url":null,"abstract":"<div><div>Obesity is an independent risk factor for heart failure with preserved ejection fraction (HFpEF). Dynamin related protein 1 (Drp1) is a key regulator of mitochondrial morphology, bioenergetics and quality control. The role of endogenous Drp1 in obesity induced HFpEF remains largely unknown. Here, adult heterozygous Drp1 floxed (Drp1^fl/+) mice were bred with αMHC-MerCreMer mice and injected with tamoxifen to induce heterogenous Drp1 knockout (hetCKO) in the heart. Control and hetCKO mice exhibited similar increases in body weight and blood glucose and developed insulin resistance after 18-week high-fat diet (HFD)-fed. HFD had no effect on cardiac contractility but induced diastolic dysfunction, fibrosis, cell death and inflammation in Control and hetCKO mice hearts. Importantly, all these adverse effects were exacerbated in the hearts of hetCKO mice, suggesting aggravated cardiac remodeling and diastolic dysfunction. HFD induced mitochondrial fission was blocked, whereas energy deficiency was exaggerated in hetCKO hearts. These effects were associated with suppressed mitochondrial quality control via mitophagy, and increased apoptosis and oxidative stress. These findings suggest that endogenous Drp1 may play an important role in limiting metabolic stress induced heart dysfunction through regulating mitophagy, oxidative stress, mitochondrial function, apoptosis, and inflammation. Our study provides critical insights into how endogenous Drp1 plays a beneficial role in metabolic stress-induced HFpEF.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102023"},"PeriodicalIF":3.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573494","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":"Inhibition of the expression of TRIM63 alleviates ventilator-induced diaphragmatic dysfunction by modulating the PPARα/PGC-1α pathway","authors":"Jun Liu ,&nbsp;Yuhan Chen ,&nbsp;Dong Han ,&nbsp;Ming Huang","doi":"10.1016/j.mito.2025.102025","DOIUrl":"10.1016/j.mito.2025.102025","url":null,"abstract":"<div><h3>Background</h3><div>Ventilator-induced diaphragmatic dysfunction (VIDD) significantly affects the prognosis of critically ill patients and has attracted considerable attention. Tripartite motif-containing protein 63 (TRIM63) plays a pivotal role in muscle protein degradation and muscle mass regulation. Its overexpression is closely associated with VIDD; however, data on the specific effects of TRIM63 on this pathological process remain insufficient.</div></div><div><h3>Objectives</h3><div>The aim of this study is to elucidate the role of TRIM63 in VIDD and to assess the correlation between the TRIM63-peroxisome proliferator activated receptor α (PPARα)/PPAR gamma coactivator (PGC-1α) pathway and mitochondrial function.</div></div><div><h3>Methods</h3><div>Specific pathogen-free grade female Wistar rats were divided into four groups: Sham + NS, Sham + MyoMed-205, MV + NS, and MV + MyoMed-205. The inhibitor group received MyoMed-205 to suppress the expression of TRIM63. After the experiment, diaphragmatic contractility, mitochondrial structure and function, oxidative stress levels, autophagy, apoptosis, and the involvement of the PPARα/PGC-1α pathway were evaluated.</div></div><div><h3>Results</h3><div>Our findings indicated that inhibiting TRIM63 prevented mechanical ventilation (MV)-induced diaphragmatic contractile dysfunction and atrophy. Mechanistically, inhibition of the expression of TRIM63 resulted in significant upregulation of the PPARα and PGC-1α expression levels, improved mitochondrial dynamics, enhanced the mitochondrial membrane potential, and reduced mitophagy and apoptosis. Structurally, inhibition of the expression of TRIM63 ameliorated MV-induced mitochondrial fragmentation, fusion, and fission.</div></div><div><h3>Conclusions</h3><div>The upregulated expression of TRIM63 in VIDD exacerbated mitochondrial damage by inhibiting the PPARα/PGC-1α signaling pathway, leading to increased reactive oxygen species, mitophagy, and apoptosis. Inhibition of the expression of TRIM63 enhanced mitochondrial function, decreased mitophagy and apoptosis, and mitigated VIDD. Thus, TRIM63 may serve as a potential target for the prevention and treatment of VIDD.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102025"},"PeriodicalIF":3.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573496","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":"The compound XueShuanTong promotes podocyte mitochondrial autophagy via the AMPK/mTOR pathway to alleviate diabetic nephropathy injury","authors":"Chuangbiao Zhang ,&nbsp;Weiwei Ren ,&nbsp;Xiaohua Lu ,&nbsp;Lie Feng ,&nbsp;Jiaying Li ,&nbsp;Beibei Zhu","doi":"10.1016/j.mito.2025.102024","DOIUrl":"10.1016/j.mito.2025.102024","url":null,"abstract":"<div><div>The study aimed to elucidate the molecular mechanisms underlying the protective effects of Compound Xueshuantong (CXst) in the context of diabetic nephropathy (DN), a major cause of kidney failure driven by podocyte injury and metabolic dysfunction. Given the critical role of the AMPK/mTOR signaling pathway in regulating cellular energy balance, autophagy, and mitochondrial health, we focused on its involvement in podocyte function and how it might be influenced by CXst. Through a series of experiments, we found that CXst treatment led to the upregulation of key proteins involved in autophagy, such as LC3 and p62, as well as proteins critical for mitochondrial function, like PGC-1α. These molecular changes helped to counteract the damaging effects of high glucose levels on podocytes, which are central to maintaining the filtration function of the kidneys. Additionally, CXst’s ability to modulate the AMPK/mTOR pathway was shown to be a pivotal factor in its protective effects, as inhibition of AMPK significantly reduced these benefits. This comprehensive study provides strong evidence that CXst exerts its protective effects against DN by modulating the AMPK/mTOR pathway, thus preserving podocyte integrity and function. These findings suggest that CXst could be a promising candidate for the development of new therapeutic strategies for the treatment of DN, offering hope for better management of this challenging condition.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102024"},"PeriodicalIF":3.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567763","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":"Research progress on paternal mitochondrial inheritance: An overview","authors":"Wen Hu ,&nbsp;Jiting Zhang ,&nbsp;Zhaoqi Wu ,&nbsp;Yi Wu ,&nbsp;Yuhui Hu ,&nbsp;Xiaohui Hu ,&nbsp;Jinguo Cao","doi":"10.1016/j.mito.2025.102019","DOIUrl":"10.1016/j.mito.2025.102019","url":null,"abstract":"<div><div>Mitochondria are self-replicating organelles with their own DNA. They play a crucial role in biological, cellular and functional processes, such as energy production, metabolism, and signal transduction. Abnormal mitochondrial function can cause various diseases such as diabetes, tumour, Parkinson’s disease, hereditary optic neuropathy, and others. Although mitochondrial functions have been extensively and widely explored, studies on mitochondrial inheritance have been limited. Mitochondrial inheritance is traditionally thought to be maternal although small amounts of paternally transmitted mitochondria have been discovered on rare occasions, and the role of paternal mitochondria transmission to offspring has been largely ignored. This review highlights the present knowledge on mitochondrial inheritance, especially the controversy and the difficulties in investigating paternal mitochondrial inheritance. More significantly, we present a comprehensive description of the physiological functions of paternal mitochondria in children and discuss the animal model to explore the mechanism of paternal mitochondrial inheritance. This review may provide a theoretical and experimental basis for improving our understanding of paternal mitochondrial inheritance, and also provide new ideas for treating mitochondrial diseases.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"82 ","pages":"Article 102019"},"PeriodicalIF":3.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria in aging and age-associated diseases","authors":"Sonu Pahal ,&nbsp;Nirjal Mainali ,&nbsp;Meenakshisundaram Balasubramaniam ,&nbsp;Robert J. Shmookler Reis ,&nbsp;Srinivas Ayyadevara","doi":"10.1016/j.mito.2025.102022","DOIUrl":"10.1016/j.mito.2025.102022","url":null,"abstract":"<div><div>Mitochondria, essential for cellular energy, are crucial in neurodegenerative disorders (NDDs) and their age-related progression. This review highlights mitochondrial dynamics, mitovesicles, homeostasis, and organelle communication. We examine mitochondrial impacts from aging and NDDs, focusing on protein aggregation and dysfunction. Prospective therapeutic approaches include enhancing mitophagy, improving respiratory chain function, maintaining calcium and lipid balance, using microRNAs, and mitochondrial transfer to protect function. These strategies underscore the crucial role of mitochondrial health in neuronal survival and cognitive functions, offering new therapeutic opportunities.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"82 ","pages":"Article 102022"},"PeriodicalIF":3.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription coupled repair occurrence in Trypanosoma cruzi mitochondria","authors":"Bruno Marçal Repolês ,&nbsp;Wesley Roger Rodrigues Ferreira ,&nbsp;Antônio Vinicius de Assis ,&nbsp;Isabela Cecília Mendes ,&nbsp;Flávia Souza Morini ,&nbsp;Camila Silva Gonçalves ,&nbsp;Carolina Moura Costa Catta-Preta ,&nbsp;Shana O. Kelley ,&nbsp;Glória Regina Franco ,&nbsp;Andrea Mara Macedo ,&nbsp;Jeremy C. Mottram ,&nbsp;Maria Cristina M. Motta ,&nbsp;Stênio Perdigão Fragoso ,&nbsp;Carlos Renato Machado","doi":"10.1016/j.mito.2025.102009","DOIUrl":"10.1016/j.mito.2025.102009","url":null,"abstract":"<div><div>Although several proteins involved in DNA repair systems have been identified in the <em>T. cruzi</em> mitochondrion, limited information is available regarding the specific DNA repair mechanisms responsible for kinetoplast DNA (kDNA) maintenance. The kDNA, contained within a single mitochondrion, exhibits a highly complex replication mechanism compared to the mitochondrial DNA of other eukaryotes. The absence of additional mitochondria makes the proper maintenance of this single mitochondrion essential for parasite viability.</div><div>Trypanosomatids possess a distinct set of proteins dedicated to kDNA organization and metabolism, known as kinetoplast-associated proteins (KAPs). Despite studies identifying the localization of these proteins, their functions remain largely unclear. Here, we demonstrate that TcKAP7 is involved in the repair of kDNA lesions induced by UV radiation and cisplatin. TcKAP7 mutant cells exhibited phenotypes similar to those observed in <em>Angomonas deanei</em> following the deletion of this gene. This monoxenic trypanosomatid colonizes the gastrointestinal tract of insects and possesses a kinetoplast with a distinct shape and kDNA topology compared to <em>T. cruzi</em>, making it a suitable comparative model in this study. Additionally, we observed that DNA damage can trigger distinct signaling pathways leading to cell death. Furthermore, we elucidated the involvement of CSB in this response, suggesting a potential interaction between TcKAP7 and CSB proteins in transcription-coupled DNA repair. The results presented here describe, for the first time, the mechanism of mitochondrial DNA repair in trypanosomatids following exposure to UV radiation and cisplatin.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102009"},"PeriodicalIF":3.9,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492763","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":"Large-scale screens identify a 19-Gene MitoScore for improved risk assessment in acute myeloid leukemia","authors":"Liting Niu ,&nbsp;Hanfei Guo ,&nbsp;Yijing Zhao","doi":"10.1016/j.mito.2025.102011","DOIUrl":"10.1016/j.mito.2025.102011","url":null,"abstract":"<div><h3>Background</h3><div>AML exhibits substantial molecular and genetic heterogeneity. Therefore, identifying key biological processes and related genes involved in the pathogenesis, as well as contributing to therapeutic resistance, is imperative for enhancing clinical outcomes. However, the assessment of mitochondrial function in AML has gradually been acknowledged but has not been widely emphasized. Hence, prioritizing the identification of mitochondrial-related biomarkers is crucial to enhance existing stratification methodologies and guide decisions on risk-adapted therapies.</div></div><div><h3>Methods</h3><div>We systematically integrated and analyzed data from nine online AML transcriptomics sequencing databases, screening the Human.MitoCarta3.0 mitochondrial gene database to identify AML-specific mitochondrial genes. A prognostic mitochondrial score was developed using LASSO regression analysis in the HOVON database as training cohort (n = 618) and validated in another eight publicly available independent cohorts (n = 1,697).</div></div><div><h3>Results</h3><div>A 19-mitochondrial function gene AML score was further generated and exhibited high prognostic power in 2,315 AML patients, named as MitoScore. MitoScore was an independent survival prognosis biomarker (p &lt; 0.001). The MitoScore effectively distinguishes several genetic abnormalities and significantly improves the ELN (European Leukemia Net) classification. Patients with a high MitoScore demonstrated a notably poor response to induction chemotherapy and related refractory AML (p &lt; 0.001). In the favorable risk gene variant and cytogenetic abnormality group, MitoScore was significantly lower compared to patients without those variants. Conversely, in the adverse group, MitoScore was significantly higher compared to patients with favorable genetic abnormalities.</div></div><div><h3>Conclusions</h3><div>Our findings underscore the utility of the MitoScore as a powerful tool for refined risk stratification and predicting chemotherapy resistance.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"82 ","pages":"Article 102011"},"PeriodicalIF":3.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471230","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}