Mitochondrion最新文献

{"title":"Kinetic characterization of respirasomes and free complex I from Yarrowia lipolytica","authors":"Giovanni García-Cruz,&nbsp;Mercedes Esparza-Perusquía,&nbsp;Alejandro Cruz-Cárdenas,&nbsp;Diana Cruz-Vilchis,&nbsp;Oscar Flores-Herrera","doi":"10.1016/j.mito.2025.102035","DOIUrl":"10.1016/j.mito.2025.102035","url":null,"abstract":"<div><div>The mitochondrion is a highly dynamic organelle capable of adapting to external stimuli and the energetic demands of the cell. As the primary source of cellular ATP, generating approximately 90 % of the total, mitochondrion facilitates the association of respiratory complexes I, III₂, and IV into supramolecular structures called respirasomes. This supramolecular organization enhances protein density within the mitochondrial inner membrane, enabling homogenous energy production. In this study, we investigate the subunits composition and the kinetic characterization of digitonin-solubilized respirasomes and the free complex I from <em>Yarrowia lipolytica</em> as well as their role in reactive oxygen species (ROS) production. The NADH:DBQ oxido reductase activity of respirasome and free complex I was similar. Respiration by respirasome was inhibited with rotenone, antimycin A, or cyanide, simultaneously to an increase in the ROS production. A value of 1.6 ± 0.2 for the NADH oxidized/oxygen reduced ratio was determined for the respirasome activity. The role of interaction between complexes in the function of the respirasome is discussed.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102035"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761044","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":"An inherited mtDNA rearrangement, mimicking a single large-scale deletion, associated with MIDD and a primary cardiological phenotype","authors":"Piervito Lopriore ,&nbsp;Andrea Legati ,&nbsp;Christiane Michaela Neuhofer ,&nbsp;Annalisa Lo Gerfo ,&nbsp;Robert Kopajtich ,&nbsp;Marco Barresi ,&nbsp;Giulia Cecchi ,&nbsp;Martin Pavlov ,&nbsp;Rossella Izzo ,&nbsp;Vincenzo Montano ,&nbsp;Maria Adelaide Caligo ,&nbsp;Riccardo Berutti ,&nbsp;Michelangelo Mancuso ,&nbsp;Holger Prokisch ,&nbsp;Daniele Ghezzi","doi":"10.1016/j.mito.2025.102037","DOIUrl":"10.1016/j.mito.2025.102037","url":null,"abstract":"<div><h3>Aim</h3><div>To identify the genetic cause in a previously unsolved pedigree, with mother and two daughters suffering of dilated cardiomyopathy with prevailing arrhythmic burden associated with diabetes mellitus and sensorineural hearing loss, without clear evidence of progressive external ophthalmoplegia.</div></div><div><h3>Methods</h3><div>Several genetic tests were performed over the years including single-gene sequencing, mitochondrial DNA (mtDNA) sequencing, NGS panel for mitochondrial diseases and cardiomyopathies, clinical exome sequencing and whole exome sequencing. Specific amplifications and long-read NGS were used to evaluate mtDNA structural alterations.</div></div><div><h3>Results</h3><div>By means of whole exome sequencing we found a novel heteroplasmic 12 kb-long single deletion in the mtDNA in all affected family members, confirmed by long-range PCR. However, a deeper investigation by long-read NGS revealed indeed the presence of rearranged mtDNA species, formed by a wild-type plus a deleted molecule. This mtDNA duplication turned out to be inherited in our pedigree and present in all tested specimens.</div></div><div><h3>Conclusion</h3><div>While mtDNA single large-scale deletions are generally considered sporadic, few old reports described maternally inherited mtDNA duplication We suggest that mtDNA large rearrangements should be considered as possible disease causes in familial cases with unusual mitochondrial phenotypes. Long-read sequencing is useful for the detection of these variants, particularly mtDNA duplications.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102037"},"PeriodicalIF":3.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753498","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":"Perceived association of mood and symptom severity in adults with mitochondrial diseases.","authors":"Catherine Kelly, Marissa Cross, Alex Junker, Kris Englestad, Xiomara Rosales, Michio Hirano, Caroline Trumpff, Martin Picard","doi":"10.1016/j.mito.2025.102033","DOIUrl":"https://doi.org/10.1016/j.mito.2025.102033","url":null,"abstract":"<p><p>Individuals with genetic mitochondrial diseases suffer from multisystem symptoms that vary in severity and over time, but the factors influencing disease manifestations are poorly understood. Based upon i) patient and family reports that stressful life events trigger or exacerbate symptoms, ii) biologically plausible pathways whereby psychological states and stress hormones influence mitochondrial energy production capacity, and iii) epidemiological literature linking traumatic/stressful life events and multiple neurologic disorders, we hypothesized that mitochondrial disease symptom severity may in part vary with daily mood. To examine patients' perception around potential psycho-biological mechanisms known to operate in other chronic illnesses, we administered the Stress, Health and Emotion Survey (SHES) to 70 adults with self-reported mitochondrial diseases. Participants rated how severe each of their symptom(s) was over the past year, separately for either 'good' (happy, calm) or 'bad' (stress, sad) emotional days. On average, patients reported that most symptoms were better on \"good\" emotional days (p < 0.0001) and worse on \"bad\" emotional days (p < 0.0001). Of the 29 symptoms assessed, 27 were associated with daily mood (p < 0.01). Some but not all symptoms were reported to be less or more severe on good and bad days, respectively, including fatigue, exercise intolerance, brain fog, and fine motor coordination (ps < 0.0001). These associative results suggest that on average individuals living with mitochondrial diseases perceive a connection between their mood and symptoms severity. These preliminary findings constitute an initial step towards developing more comprehensive models of the psychobiological factors that influence the course of mitochondrial diseases.</p>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":" ","pages":"102033"},"PeriodicalIF":3.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753436","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":"Therapeutic potential of DDQ in enhancing mitochondrial health and cognitive function in Late-Onset Alzheimer’s disease","authors":"Sudhir Kshirsagar ,&nbsp;Rainier Vladlen Alvir ,&nbsp;Jangampalli Adi Pradeepkiran ,&nbsp;Arubala P. Reddy ,&nbsp;P. Hemachandra Reddy","doi":"10.1016/j.mito.2025.102036","DOIUrl":"10.1016/j.mito.2025.102036","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, mitochondrial dysfunction, and neuroinflammation. This study evaluates the therapeutic potential of DDQ, a small molecule in the humanized Abeta knockin (hAbKI) mice that represents late-onset AD. Our findings demonstrate that DDQ treatment significantly improves cognitive performance as assessed through behavioral tests, including the rotarod, open field, Y-maze, and Morris water maze, compared to untreated hAbKI mice. At the molecular level, DDQ promoted mitochondrial biogenesis, as evidenced by enhanced expression of key proteins like PGC1α, NRF1, and TFAM. Additionally, DDQ treatment facilitated mitophagy, as indicated by elevated levels of PINK1 and Parkin, and reduced neuroinflammation, reflected by decreased Iba1 and GFAP levels. Transmission electron microscopy analysis revealed a marked improvement in mitochondrial morphology, with increased mitochondrial length and reduced mitochondrial numbers in DDQ-treated mice. Furthermore, DDQ treatment led to an increase in mitophagic vacuoles, suggesting that it effectively removes dysfunctional mitochondria. Taken together, for the first time, our study results support the potential of DDQ as a promising neuroprotective agent for late-onset AD, addressing mitochondrial dysfunction, neuroinflammation, and cognitive decline. Our study focused on developing small molecules that modulate mitophagy, mitochondrial dynamics and neuroinflammatory pathways for aging, AD and other neurodegenerative disorders.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102036"},"PeriodicalIF":3.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738243","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":"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}