Mitochondrion最新文献

{"title":"Decoding mitochondrial quality control mechanisms: Identifying treatment targets for enhanced cellular health","authors":"Nitu L. Wankhede ,&nbsp;Spandana Rajendra Kopalli ,&nbsp;Mrunali D. Dhokne ,&nbsp;Dishant J. Badnag ,&nbsp;Pranali A. Chandurkar ,&nbsp;Shubhada V. Mangrulkar ,&nbsp;Prajwali V. Shende ,&nbsp;Brijesh G. Taksande ,&nbsp;Aman B. Upaganlawar ,&nbsp;Milind J. Umekar ,&nbsp;Sushruta Koppula ,&nbsp;Mayur B. Kale","doi":"10.1016/j.mito.2024.101926","DOIUrl":"10.1016/j.mito.2024.101926","url":null,"abstract":"<div><p>Mitochondria are singular cell organelles essential for many cellular functions, which includes responding to stress, regulating calcium levels, maintaining protein homeostasis, and coordinating apoptosis response. The vitality of cells, therefore, hinges on the optimal functioning of these dynamic organelles. Mitochondrial Quality Control Mechanisms (MQCM) play a pivotal role in ensuring the integrity and functionality of mitochondria. Perturbations in these mechanisms have been closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Compelling evidence suggests that targeting specific pathways within the MQCM could potentially offer a therapeutic avenue for rescuing mitochondrial integrity and mitigating the progression of neurodegenerative diseases. The intricate interplay of cellular stress, protein misfolding, and impaired quality control mechanisms provides a nuanced understanding of the underlying pathology. Consequently, unravelling the specific MQCM dysregulation in neurodegenerative disorders becomes paramount for developing targeted therapeutic strategies. This review delves into the impaired MQCM pathways implicated in neurodegenerative disorders and explores emerging therapeutic interventions. By shedding light on pharmaceutical and genetic manipulations aimed at restoring MQCM efficiency, the discussion aims to provide insights into novel strategies for ameliorating the progression of neurodegenerative diseases. Understanding and addressing mitochondrial quality control mechanisms not only underscore their significance in cellular health but also offer a promising frontier for advancing therapeutic approaches in the realm of neurodegenerative disorders.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101926"},"PeriodicalIF":3.9,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469426","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 transcription and mitochondrial genome-encoded long noncoding RNA in diabetic retinopathy","authors":"Jay Kumar,&nbsp;Renu A. Kowluru","doi":"10.1016/j.mito.2024.101925","DOIUrl":"10.1016/j.mito.2024.101925","url":null,"abstract":"<div><p>In diabetic retinopathy, mitochondrial DNA (mtDNA) is damaged and mtDNA-encoded genes and long noncoding RNA <em>cytochrome B</em> (Lnc<em>CytB)</em> are downregulated. LncRNAs lack an open reading frame, but they can regulate gene expression by associating with DNA/RNA/protein. Double stranded mtDNA has promoters on both heavy (<em>HSP</em>) and light (<em>LSP</em>) strands with binding sites for mitochondrial transcription factor A (TFAM) between them. The aim was to investigate the role of Lnc<em>CytB</em> in mtDNA transcription in diabetic retinopathy. Using human retinal endothelial cells incubated in high glucose, the effect of regulation of Lnc<em>CytB</em> on TFAM binding at mtDNA promoters was investigated by Chromatin immunoprecipitation, and binding of Lnc<em>CytB</em> at TFAM by RNA immunoprecipitation and RNA fluorescence <em>in situ</em> hybridization. High glucose decreased TFAM binding at both <em>HSP</em> and <em>LSP</em>, and binding of Lnc<em>CytB</em> at TFAM. While Lnc<em>CytB</em> overexpression ameliorated decrease in TFAM binding and transcription of genes encoded by both H- and L- strands, Lnc<em>CytB-</em>siRNA further downregulated them. Maintenance of mitochondrial homeostasis by overexpressing mitochondrial superoxide dismutase or <em>Sirtuin-1</em> protected diabetes-induced decrease in TFAM binding at mtDNA and Lnc<em>CytB</em> binding at TFAM, and mtDNA transcription. Similar results were obtained from mouse retinal microvessels from streptozotocin-induced diabetic mice. Thus, Lnc<em>CytB</em> facilitates recruitment of TFAM at <em>HSP</em> and <em>LSP</em>, and its downregulation in diabetes compromises the binding, resulting in the downregulation of polypeptides encoded by mtDNA. Regulation of Lnc<em>CytB</em>, in addition to protecting mitochondrial genomic stability, should also help in maintaining the transcription of mtDNA encoded genes and electron transport chain integrity in diabetic retinopathy.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101925"},"PeriodicalIF":3.9,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469427","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":"mitoPADdb: A database of mitochondrial proteins associated with diseases","authors":"Jagannath Das ,&nbsp;Sudipto Bhattacharjee ,&nbsp;Sudipto Saha","doi":"10.1016/j.mito.2024.101927","DOIUrl":"10.1016/j.mito.2024.101927","url":null,"abstract":"<div><p>Mitochondrial protein/gene mutations and expression variations contribute to the pathogenesis of various diseases, such as neurodegenerative and metabolic diseases. Detailed studies on mitochondrial protein-encoding (MPE) genes across diseases can provide clues for novel therapeutic strategies. Here, we collected, compiled, and manually curated the MPE gene mutation and expression variations data and their association with diseases in a single platform named mitoPADdb. The database contains 810 genes with 18,356 mutations and 1284 qualitative expression variations associated with 1793 diseases, grouped into 15 categories. It allows users to perform a comparative quantitative gene expression analysis for 317 transcriptomic studies across disease categories. Further, it provides information on MPE genes-associated molecular pathways. The mitoPADdb is a valuable resource for investigating mitochondrial dysfunction-related diseases. It can be accessed via <span><u>http://bicresources.jcbose.ac.in/ssaha4/mitopaddb/index.html</u></span><svg><path></path></svg>.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101927"},"PeriodicalIF":3.9,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469428","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":"Role of mitochondrial homeostasis in D-galactose-induced cardiovascular ageing from bench to bedside","authors":"Yogita Sahu,&nbsp;Pratiksha Jamadade,&nbsp;Krushna Ch Maharana,&nbsp;Sanjiv Singh","doi":"10.1016/j.mito.2024.101923","DOIUrl":"10.1016/j.mito.2024.101923","url":null,"abstract":"<div><p>Ageing is an inevitable phenomenon which affects the cellular to the organism level in the progression of the time. Oxidative stress and inflammation are now widely regarded as the key processes involved in the aging process, which may then cause significant harm to mitochondrial DNA, leading to apoptosis. Normal circulatory function is a significant predictor of disease-free life expectancy. Indeed, disorders affecting the cardiovascular system, which are becoming more common, are the primary cause of worldwide morbidity, disability, and mortality. Cardiovascular aging may precede or possibly underpin overall, age-related health decline. Numerous studies have found<!--> <!-->mitochondrial mechanistc approach<!--> <!-->plays a vital role in the in the onset and development of aging. The D-galactose (D-gal)-induced aging model is well recognized and commonly used in the aging study. In this review we redeposit the association of the previous and current studies on mitochondrial homeostasis and its underlying mechanisms in D-galactose cardiovascular ageing. Further we focus the novel and the treatment strategies to combat the major complication leading to the cardiovascular ageing.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101923"},"PeriodicalIF":3.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457934","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":"Beyond the membrane: Exploring non-viral methods for mitochondrial gene delivery","authors":"Dilpreet Singh","doi":"10.1016/j.mito.2024.101922","DOIUrl":"10.1016/j.mito.2024.101922","url":null,"abstract":"<div><p>Mitochondrial disorders, stemming from mutations in mitochondrial DNA (mtDNA), present a significant therapeutic challenge due to their complex pathophysiology and broad spectrum of clinical manifestations. Traditional gene therapy approaches, primarily reliant on viral vectors, face obstacles such as potential immunogenicity, insertional mutagenesis, and the specificity of targeting mtDNA. This review delves into non-viral methods for mitochondrial gene delivery, emerging as a promising alternative to overcome these limitations. Focusing on lipid-based nanoparticles, polymer-based vectors, and mitochondrial-targeted peptides, the mechanisms of action, advantages, and current applications in treating mitochondrial diseases was well elucidated. Non-viral vectors offer several benefits, including reduced immunogenicity, enhanced safety profiles, and the flexibility to carry a wide range of genetic material. We examine case studies where these methods have been applied, highlighting their potential in correcting pathogenic mtDNA mutations and mitigating disease phenotypes. Despite their promise, challenges such as delivery efficiency, specificity, and long-term expression stability persist. The review underscores the need for ongoing research to refine these delivery systems carry a wide range of genetic material. We examine case studies where these methods settings. As we advance our understanding of mitochondrial biology and gene delivery technologies, non-viral methods hold the potential to revolutionize the treatment of mitochondrial disorders, offering hope for therapies that can precisely target and correct the underlying genetic defects.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101922"},"PeriodicalIF":4.4,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427199","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":"Escherichia coli infection induces ferroptosis in bovine mammary epithelial cells by activating the Wnt/β-catenin pathway-mediated mitophagy","authors":"Cuicui Zhuang ,&nbsp;Yang Liu ,&nbsp;Herman W. Barkema ,&nbsp;Zhaoju Deng ,&nbsp;Jian Gao ,&nbsp;John P. Kastelic ,&nbsp;Bo Han ,&nbsp;Jianhai Zhang","doi":"10.1016/j.mito.2024.101921","DOIUrl":"10.1016/j.mito.2024.101921","url":null,"abstract":"<div><p>Iron overload causes mitochondrial damage, and then activates mitophagy, which may directly trigger and amplify ferroptosis. Our objective was to investigate whether <em>Escherichia coli</em> (<em>E. coli</em>) isolated from clinical bovine mastitis induces ferroptosis in bovine mammary epithelial cells (bMECs) and if so, the underlying regulatory mechanism. <em>E. coli</em> infection caused mitochondrial damage, mitophagy, and ferroptosis. Rapamycin and chloroquine increased and suppressed ferroptosis, respectively, in <em>E. coli</em>-treated bMECs. Moreover, <em>E. coli</em> infection activated the Wnt/β-catenin pathway, but foscenvivint alleviated it. In conclusion, <em>E. coli</em> infection induced ferroptosis through activation of the Wnt/β-catenin pathway-promoted mitophagy, and it also suppressed GPX4 expression.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101921"},"PeriodicalIF":4.4,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141391117","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":"Increased expression of SLC25A18 is associated with Alzheimer’s disease and is involved in Aβ42-induced mitochondrial dysfunction and apoptosis in neuronal cells","authors":"Jia-Yi Song ,&nbsp;Yong Jia ,&nbsp;Hao Han ,&nbsp;Xue-Han Yang ,&nbsp;Jing Zhang ,&nbsp;Qiang Zhang ,&nbsp;Su-Shan Wang ,&nbsp;Chun-Yan Wang ,&nbsp;Li Chen ,&nbsp;Ming Zhang","doi":"10.1016/j.mito.2024.101918","DOIUrl":"10.1016/j.mito.2024.101918","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is currently one of the most serious public health concerns in the world. However, the best approach to treat AD has yet to be discovered, implying that we must continue to work hard to find new AD target genes. In this study, we further analysed Gene Expression Omnibus (GEO) data and discovered that the expression of the Mitochondria glutamate carrier SLC25A18 is associated with AD by screening the differentially expressed genes in different regions of the brains of Alzheimer’s disease patients. To verify the expression of SLC25A18 during Alzheimer’s disease development, we analysed animal models (5×FAD transgenic AD animal model, chemically induced AD animal model, natural ageing animal model), and the results showed that the expression of SLC25A18 was increased in animal models of AD. Further investigation of the different regions found that SLC25A18 expression was elevated in the EC, TeA, and CA3, and expressed in neurons. Next, We found that Aβ42 treatment elevated SLC25A18 expression in Neuro 2A cells. Reducing SLC25A18 expression attenuated mitochondrial dysfunction and neuronal apoptosis caused by Aβ42. Overexpression of SLC25A18 increased ATP and intracellular superoxide anions but decreased mitochondrial membrane potential. The results indicate that SLC25A18 affects mitochondrial function and neuronal apoptosis, and is related to AD, which makes it a potential target for treating brain dysfunction.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101918"},"PeriodicalIF":4.4,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S156772492400076X/pdfft?md5=a6d038576477b989162d7b765a2d4446&pid=1-s2.0-S156772492400076X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317690","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":"The interplay between mitophagy and mitochondrial ROS in acute lung injury","authors":"Yizhi Zhong ,&nbsp;Siwei Xia ,&nbsp;Gaojian Wang ,&nbsp;Qinxue Liu ,&nbsp;Fengjie Ma ,&nbsp;Yijin Yu ,&nbsp;Yaping Zhang ,&nbsp;Lu Qian ,&nbsp;Li Hu ,&nbsp;Junran Xie","doi":"10.1016/j.mito.2024.101920","DOIUrl":"10.1016/j.mito.2024.101920","url":null,"abstract":"<div><p>Mitochondria orchestrate the production of new mitochondria and the removal of damaged ones to dynamically maintain mitochondrial homeostasis through constant biogenesis and clearance mechanisms. Mitochondrial quality control particularly relies on mitophagy, defined as selective autophagy with mitochondria-targeting specificity. Most ROS are derived from mitochondria, and the physiological concentration of mitochondrial ROS (mtROS) is no longer considered a useless by-product, as it has been proven to participate in immune and autophagy pathway regulation. However, excessive mtROS appears to be a pathogenic factor in several diseases, including acute lung injury (ALI). The interplay between mitophagy and mtROS is complex and closely related to ALI. Here, we review the pathways of mitophagy, the intricate relationship between mitophagy and mtROS, the role of mtROS in the pathogenesis of ALI, and their effects and related progression in ALI induced by different conditions.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101920"},"PeriodicalIF":3.9,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321214","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":"Thyroid hormone enhances efficacy of cisplatin in lung cancer patients via down-regulating GLUT1 expression and reversing the Warburg effect","authors":"Chenchen Fan ,&nbsp;Yanbei Ren ,&nbsp;Wen Zhang ,&nbsp;Jing Wen ,&nbsp;Wenjia Zhang ,&nbsp;Shumeng Lin ,&nbsp;Yidong Bai ,&nbsp;Tiansheng Zheng ,&nbsp;Baigenzhin Abay ,&nbsp;Ming Li ,&nbsp;Lihong Fan","doi":"10.1016/j.mito.2024.101919","DOIUrl":"10.1016/j.mito.2024.101919","url":null,"abstract":"<div><p>Cisplatin (CDDP) is a standard non-small cell lung cancer (NSCLC) chemotherapy, but its efficacy is hampered by resistance, partly due to the Warburg effect. This study investigates how thyroid hormones enhance the Warburg effect, increasing sensitivity to cisplatin in lung cancer. Clinical data from advanced NSCLC patients were analyzed based on thyroid hormone levels, categorizing patients into high and low groups. Cellular experiments involved Control, 10uM CDDP, 10uM CDDP + 0.1uM T3, and 10uM CDDP + 0.1uM T4 categories. Parameters were measured in A549 and PC9 lung cancer cells, including proliferation, apoptosis, mitochondrial membrane potential, ROS production, glycolysis enzyme activity, lactic acid level, and ATP content. Gene and protein expressions were assessed using qPCR and Western Blot. Analysis revealed higher FT3 levels correlated with prolonged progression-free survival before chemotherapy (median PFS: high FT3 group = 12.67 months, low FT3 group = 7.03 months, p = 0.01). Cellular experiments demonstrated that thyroid hormones increase lung cancer cell sensitivity to cisplatin, inhibiting proliferation and enhancing efficacy. The mechanism involves thyroid hormones and cisplatin jointly down-regulating MSI1/AKT/GLUT1 expression, reducing lactic acid and glycolysis. This Warburg effect reversal boosts ATP levels, elevates ROS, and decreases MMP, enhancing cisplatin effectiveness in A549 and PC9 cells. In conclusion, elevated free T3 levels in advanced NSCLC patients correlate with prolonged progression-free survival under cisplatin chemotherapy. Cellular experiments reveal that thyroid hormones enhance lung cancer cell sensitivity to cisplatin by reversing the Warburg effect, providing a mechanistic basis for improved therapeutic outcomes.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101919"},"PeriodicalIF":3.9,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321215","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 role of mitochondrial genes in ischemia-reperfusion injury: A systematic review of experimental studies","authors":"Zeyu Chen ,&nbsp;Daniel Rayner ,&nbsp;Robert Morton ,&nbsp;Laura Banfield ,&nbsp;Guillaume Paré ,&nbsp;Michael Chong","doi":"10.1016/j.mito.2024.101908","DOIUrl":"10.1016/j.mito.2024.101908","url":null,"abstract":"<div><p>Mitochondrial dysfunction contributes to pathological conditions like ischemia–reperfusion (IR) injury. To address the lack of effective therapeutic interventions for IR injury and potential knowledge gaps in the current literature, we systematically reviewed 3800 experimental studies across 5 databases and identified 20 mitochondrial genes impacting IR injury in various organs. Notably, <em>CyPD, Nrf2,</em> and <em>GPX4</em> are well-studied genes consistently influencing IR injury outcomes. Emerging genes like <em>ALDH2, BNIP3,</em> and <em>OPA1</em> are supported by human genetic evidence, thereby warranting further investigation. Findings of this review can inform future research directions and inspire therapeutic advancements.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101908"},"PeriodicalIF":4.4,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924000667/pdfft?md5=d2423e2c09b93620a942ba7e3ae8febf&pid=1-s2.0-S1567724924000667-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288320","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}