Mitochondrion最新文献

{"title":"Pyridoxal-5-phosphate mitigates age-related metabolic imbalances in the rat heart through the H2S/AKT/GSK3β signaling axis","authors":"Nataliia A. Strutynska ,&nbsp;Volodymyr V. Balatskyi ,&nbsp;Ruslan B. Strutynskyi ,&nbsp;Yulia V. Goshovska ,&nbsp;Lidiia A. Mys ,&nbsp;Alina Yu. Luchkova ,&nbsp;Maiia V. Denysova ,&nbsp;Yuliia P. Korkach ,&nbsp;Vladyslav R. Strutynskyi ,&nbsp;Oksana O. Piven ,&nbsp;Pawel Dobrzyn ,&nbsp;Vadym F. Sagach","doi":"10.1016/j.mito.2024.102001","DOIUrl":"10.1016/j.mito.2024.102001","url":null,"abstract":"<div><div>Pyridoxal-5-phosphate (PLP) enhances the synthesis of endogenous hydrogen sulfide, a potent regulator of cell metabolism. We used 24-month-old rats to investigate the PLP mitoprotective function in the aging heart. We demonstrated improvement of mitochondrial bioenergetic functions, inhibition of mPTP opening after PLP administration. Moreover, PLP treatment increased glucose consumption and utilization, decreased lipid transport into the cells, but increased fatty acid β-oxidation, providing sufficient energy. An ECG study showed a significant improvement in cardiac function in PLP-treated old rats. Our data suggest that PLP may exert its effect through the H₂S/AKT/GSK3β axis with further targeting of the Sirt1/PGC-1α signaling pathway.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"81 ","pages":"Article 102001"},"PeriodicalIF":3.9,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927572","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 DNA variants and dysfunction in the pathogenesis and progression of multiple sclerosis","authors":"Ramyar Rahimi Darehbagh ,&nbsp;Shaghayegh Khanmohammadi ,&nbsp;Nima Rezaei","doi":"10.1016/j.mito.2024.102002","DOIUrl":"10.1016/j.mito.2024.102002","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). The etiology of MS remains elusive, with a complex interplay of genetic and environmental factors contributing to its pathogenesis. Recent studies showed mitochondrial DNA (mtDNA) as a potential player in the development and progression of MS. These studies encompassed mtDNA variants, copy number variations, and haplogroups. This narrative review aims to synthesize the current understanding of the role of mtDNA’s in MS. The findings of this review suggest that mtDNA may indeed play a role in the development and progression of MS. Several studies have reported an association between mtDNA variants and increased susceptibility to MS, while others have found a link between mtDNA copy number variations and disease severity. Furthermore, specific mtDNA haplogroups have been demonstrated to confer protection against MS. MtDNA alterations may make neurons and oligodendrocytes more susceptible to inflammatory and oxidative stress, causing demyelination and axonal degeneration in MS patients. In conclusion, this review underscores the potential significance of mtDNA in the pathogenesis of MS and highlights the need for further research to fully elucidate its role. A deeper understanding of mtDNA’s involvement in MS may pave the way for the development of novel therapeutic strategies to combat this debilitating disease.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"81 ","pages":"Article 102002"},"PeriodicalIF":3.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896136","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":"Autologous mitochondrial transplantation enhances the bioenergetics of auditory cells and mitigates cell loss induced by H2O2","authors":"Mustafa Nazir Okur ,&nbsp;Adam Ratajczak ,&nbsp;Arash Kheradvar ,&nbsp;Hamid R Djalilian","doi":"10.1016/j.mito.2024.102003","DOIUrl":"10.1016/j.mito.2024.102003","url":null,"abstract":"<div><div>Hearing loss is a widespread and disabling condition with no current cure, underscoring the urgent need for new therapeutic approaches for treatment and prevention. A recent mitochondrial therapy approach by introducing exogenous mitochondria to the cells has shown promising results in mitigating mitochondria-related disorders. Despite the essential role of mitochondria in hearing, this novel strategy has not yet been tested for the treatment of hearing loss. More importantly, whether cochlear cells take up exogenous mitochondria and its consequence on cell bioenergetics has never been tested before. Here, we showed that exogenous mitochondria from HEI-OC1 auditory cells internalize into a new set of HEI-OC1 cells through co-incubation in a dose-dependent manner without inducing toxicity. We observed that auditory cells that received exogenous mitochondria exhibited increased bioenergetics compared to the controls that received none. Furthermore, we found that mitochondrial transplantation protects cells from oxidative stress and H₂O₂-induced apoptosis, while partially restoring bioenergetics diminished by H₂O₂ exposure. These findings support initial evidence for the feasibility and potential advantages of mitochondrial therapy in auditory cells. If successful in animal models and ultimately in humans, this novel therapy offers prominent potential for the treatment of sensorineural hearing loss.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"81 ","pages":"Article 102003"},"PeriodicalIF":3.9,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100904","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":"Substitution of leucine by glutamate perturbs VopE localization to mitochondria: Lessons from yeast model system","authors":"Nandita Sharma ,&nbsp;Kiran Heer ,&nbsp;Saumya Raychaudhuri","doi":"10.1016/j.mito.2024.101999","DOIUrl":"10.1016/j.mito.2024.101999","url":null,"abstract":"<div><div>VopE, a type III effector protein of <em>Vibrio cholerae</em>, modulates host mitochondrial function. Mitochondrial entry of VopE is directly linked with an N-terminal precursor sequence known as the mitochondrial targeting sequence or MTS. MTS of VopE is constituted with 23 amino acids. Earlier studies have shown the importance of leucine residue at position 4 in VopE translocation to mitochondria. In the present study, we have identified another leucine residue at position 15 contributing to the mitochondrial uptake of VopE in the yeast model system. Substitution of leucine¹⁵ with glutamate decreases mitochondrial localization and toxicity of the mutants.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"81 ","pages":"Article 101999"},"PeriodicalIF":3.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829441","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":"Mitochondria-targeted nanotherapeutics: A new frontier in neurodegenerative disease treatment","authors":"Nishad Keethedeth,&nbsp;Rajesh Anantha Shenoi","doi":"10.1016/j.mito.2024.102000","DOIUrl":"10.1016/j.mito.2024.102000","url":null,"abstract":"<div><div>Mitochondria are the seat of cellular energy and play key roles in regulating several cellular processes such as oxidative phosphorylation, respiration, calcium homeostasis and apoptotic pathways. Mitochondrial dysfunction results in error in oxidative phosphorylation, redox imbalance, mitochondrial DNA mutations, and disturbances in mitochondrial dynamics, all of which can lead to several metabolic and degenerative diseases. A plethora of studies have provided evidence for the involvement of mitochondrial dysfunction in the pathogenesis of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Hence mitochondria have been used as possible therapeutic targets in the regulation of neurodegenerative diseases. However, the double membranous structure of mitochondria poses an additional barrier to most drugs even if they are able to cross the plasma membrane. Most of the drugs acting on mitochondria also required very high doses to exhibit the desired mitochondrial accumulation and therapeutic effect which in-turn result in toxic effects. Mitochondrial targeting has been improved by direct conjugation of drugs to mitochondriotropic molecules like dequalinium (DQA) and triphenyl phosphonium (TPP) cations. But being cationic in nature, these molecules also exhibit toxicity at higher doses. In order to further improve the mitochondrial localization with minimal toxicity, TPP was conjugated with various nanomaterials like liposomes. inorganic nanoparticles, polymeric nanoparticles, micelles and dendrimers. This review provides an overview of the role of mitochondrial dysfunction in neurodegenerative diseases and various nanotherapeutic strategies for efficient targeting of mitochondria-acting drugs in these diseases.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"81 ","pages":"Article 102000"},"PeriodicalIF":3.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813853","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 (mtDNA) accelerates oxygen-glucose deprivation-induced injury of proximal tubule epithelia cell via inhibiting NLRC5","authors":"Guojun Ge ,&nbsp;Bocheng Zhu ,&nbsp;Xiaofeng Zhu ,&nbsp;Zhenfei Yu ,&nbsp;Keqing Zhu ,&nbsp;Mengshi Cheng","doi":"10.1016/j.mito.2024.101989","DOIUrl":"10.1016/j.mito.2024.101989","url":null,"abstract":"<div><div>The high morbidity and mortality associated with acute kidney injury (AKI) are global health concerns. AKI is commonly attributed to ischemia/reperfusion injury (IRI), a condition characterized by activation of inflammatory responses and mitochondrial dysfunction. Nonetheless, mitochondrial DNA (mtDNA) has the potential to induce renal IRI. This study aimed to elucidate the mechanism and function of mtDNA in HK-2 cells that had been exposed to oxygen-glucose deprivation/reperfusion (OGD/R) and in renal IRI mice. OGD/R was discovered to induce an increase in the amount of mtDNA in HK-2 cells. Moreover, our study demonstrated that mtDNA facilitated cellular apoptosis and inflammation <em>in vivo</em> and <em>in vitro</em>. Given the potential role of inflammation in OGD/R, we investigated the effect of mtDNA on various signaling pathways associated with inflammation. Western blot analysis demonstrated that mtDNA significantly upregulated <em>NLRC5</em>/<em>TAP1</em> signaling. Furthermore, the upregulation of <em>NLRC5</em> and <em>TAP1</em> expression induced by mtDNA was reversed when <em>NLRC5</em> was inhibited. It is worth mentioning that the loss of <em>NLRC5</em> effectively nullified the beneficial effects of mtDNA on inflammation and cell apoptosis induced by OGD/R. In addition, in renal IRI mice, mtDNA treatment also aggravated inflammation and kidney damage, and increased the <em>NLRC5</em> levels in kidney tissues. These results suggested that <em>NLRC5</em> acts as an intermediary between mtDNA and the pathogenicity of renal IRI. In summary, this study provides evidence that mtDNA promotes apoptosis and inflammation in OGD/R treated HK-2 cells and renal IRI mice through upregulating <em>NLRC5</em> levels.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"81 ","pages":"Article 101989"},"PeriodicalIF":3.9,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716272","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":"Expression of fragmented ribosomal RNA from the mitochondrial genome of Eimeria tenella","authors":"Perryn S. Kruth ,&nbsp;Chloe MacNeil ,&nbsp;John R. Barta","doi":"10.1016/j.mito.2024.101990","DOIUrl":"10.1016/j.mito.2024.101990","url":null,"abstract":"<div><div>Highly fragmented ribosomal RNA-coding sequences are characteristic of mitogenomes of protozoan parasites of the phylum Apicomplexa. Identification of ribosomal RNA encoding sequences in apicomplexan mitogenomes has largely relied on sequence similarity with several apicomplexan species for which expression of these genes has been demonstrated. The present study applied Next-Gen sequencing to investigate the expression of fragmented putative mitochondrial rRNAs in<!--> <em>Eimeria tenella</em>, a coccidian parasite of poultry.</div><div>Expression of 18 of 19 putative rDNA fragments included in the original published<!--> <em>E. tenella</em> <!-->mitogenome was confirmed. Sequence comparison with<!--> <em>Plasmodium falciparum</em> <!-->and NGS identified 14 additional putative fragments. Two small RNAs were identified that did not share sequence similarities with other known rDNA sequences. Eight sRNAs were identified that represented smaller chunks of putative rDNA fragments and three were observed that represented two putative rDNA fragments (i.e., polycistronic transcripts). Relative abundances of each sRNA species ranged across three orders of magnitude. Twenty-five of the 45 distinct sRNAs expressed from the mitogenome were polyadenylated in more than 50% of instances.</div><div>The identification of unique sRNAs without significant homology to known sequences and the observation of polycistronic transcripts highlight the complexity of regulation of expression of the<!--> <em>E.<!--> <!-->tenella<!--> </em>mitogenome. The varied relative abundances, presence of shorter RNAs expressed from longer putative rDNA fragments, and variable polyadenylation of these sRNAs highlight additional areas for future work towards better understanding the expression of the mitogenome in this important poultry pathogen. More generally, these findings expand our wider understanding of evolution of apicomplexan mitogenomes.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"81 ","pages":"Article 101990"},"PeriodicalIF":3.9,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716271","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 abundance and circulating metabolomic profiling: Multivariable-adjusted and Mendelian randomization analyses in UK Biobank","authors":"Jiao Luo ,&nbsp;Saskia le Cessie ,&nbsp;Ko Willems van Dijk ,&nbsp;Sara Hägg ,&nbsp;Felix Grassmann ,&nbsp;Diana van Heemst ,&nbsp;Raymond Noordam","doi":"10.1016/j.mito.2024.101991","DOIUrl":"10.1016/j.mito.2024.101991","url":null,"abstract":"<div><h3>Background</h3><div>Low leukocyte mitochondrial DNA (mtDNA) abundance has been associated with a higher risk of atherosclerotic cardiovascular disease, but through unclear mechanisms. We aimed to investigate whether low mtDNA abundance is associated with worse metabolomic profiling, as being potential intermediate phenotypes, using cross-sectional and genetic studies.</div></div><div><h3>Methods</h3><div>Among 61,186 unrelated European participants from UK Biobank, we performed multivariable-adjusted linear regression analyses to examine the associations between mtDNA abundance and 168 NMR-based circulating metabolomic measures and nine metabolomic principal components (PCs) that collectively covered 91.5% of the total variation of individual metabolomic measures. Subsequently, we conducted Mendelian randomization (MR) to approximate the causal effects of mtDNA abundance on the individual metabolomic measures and their metabolomic PCs.</div></div><div><h3>Results</h3><div>After correction for multiple testing, low mtDNA abundance was associated with 130 metabolomic measures, predominantly lower concentrations of some amino acids and higher concentrations of lipids, lipoproteins and fatty acids; moreover, mtDNA abundance was associated with seven out of the nine metabolomic PCs. Using MR, genetically-predicted low mtDNA abundance was associated with lower lactate (standardized beta and 95% confidence interval: −0.17; −0.26, −0.08), and higher acetate (0.15; 0.07,0.23), and unsaturation degree (0.14; 0.08,0.20). Similarly, genetically-predicted low mtDNA abundance was associated with lower metabolomic PC2 (related to lower concentrations of lipids and fatty acids), and higher metabolomic PC9 (related to lower concentrations of glycolysis-related metabolites).</div></div><div><h3>Conclusion</h3><div>Low mtDNA abundance is associated with metabolomic perturbations, particularly reflecting a pro-atherogenic metabolomic profile, which potentially could link low mtDNA abundance to higher atherosclerosis risk.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"80 ","pages":"Article 101991"},"PeriodicalIF":3.9,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730282","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":"Scientific investigation of non-coding RNAs in mitochondrial epigenetic and aging disorders: Current nanoengineered approaches for their therapeutic improvement","authors":"Vaibhav Patange ,&nbsp;Kailash Ahirwar ,&nbsp;Tripti Tripathi ,&nbsp;Pratima Tripathi ,&nbsp;Rahul Shukla","doi":"10.1016/j.mito.2024.101979","DOIUrl":"10.1016/j.mito.2024.101979","url":null,"abstract":"<div><div>Genetic control is vital for the growth of cells and tissues, and it also helps living things, from single-celled organisms to complex creatures, maintain a stable internal environment. Within cells, structures called mitochondria act like tiny power plants, producing energy and keeping the cell balanced. The two primary categories of RNA are messenger RNA (mRNA) and non-coding RNA (ncRNA). mRNA carries the instructions for building proteins, while ncRNA does various jobs at the RNA level. There are different kinds of ncRNA, each with a specific role. Some help put RNA molecules together correctly, while others modify other RNAs or cut them into smaller pieces. Still others control how much protein is made from a gene. Scientists have recently discovered many more ncRNAs than previously known, and their functions are still being explored. This article analyzes the RNA molecules present within mitochondria, which have a crucial purpose in the operation of mitochondria. We’ll also discuss how genes can be turned on and off without changing their DNA code, and how this process might be linked to mitochondrial RNA. Finally, we’ll explore how scientists are using engineered particles to silence genes and develop new treatments based on manipulating ncRNA.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"80 ","pages":"Article 101979"},"PeriodicalIF":3.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591231","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 multifaceted modulation of mitochondrial metabolism in tumorigenesis","authors":"Keerthiga Rajendiran ,&nbsp;Yafang Xie ,&nbsp;De-Sheng Pei ,&nbsp;Ailing Fu","doi":"10.1016/j.mito.2024.101977","DOIUrl":"10.1016/j.mito.2024.101977","url":null,"abstract":"<div><div>Changes in mitochondrial metabolism produce a malignant transformation from normal cells to tumor cells. Mitochondrial metabolism, comprising bioenergetic metabolism, biosynthetic process, biomolecular decomposition, and metabolic signal conversion, obviously forms a unique sign in the process of tumorigenesis. Several oncometabolites produced by mitochondrial metabolism maintain tumor phenotype, which are recognized as tumor indicators. The mitochondrial metabolism synchronizes the metabolic and genetic outcome to the potent tumor microenvironmental signals, thereby further promoting tumor initiation. Moreover, the bioenergetic and biosynthetic metabolism within tumor mitochondria orchestrates dynamic contributions toward cancer progression and invasion. In this review, we describe the contribution of mitochondrial metabolism in tumorigenesis through shaping several hallmarks such as microenvironment modulation, plasticity, mitochondrial calcium, mitochondrial dynamics, and epithelial-mesenchymal transition. The review will provide a new insight into the abnormal mitochondrial metabolism in tumorigenesis, which will be conducive to tumor prevention and therapy through targeting tumor mitochondria.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"80 ","pages":"Article 101977"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591232","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}