Mitochondrion最新文献

{"title":"Multifaceted role of dynamin-related protein 1 in cardiovascular disease: From mitochondrial fission to therapeutic interventions","authors":"Satinder Kaur ,&nbsp;Naina Khullar ,&nbsp;Umashanker Navik ,&nbsp;Anjana Bali ,&nbsp;Gurjit Kaur Bhatti ,&nbsp;Jasvinder Singh Bhatti","doi":"10.1016/j.mito.2024.101904","DOIUrl":"10.1016/j.mito.2024.101904","url":null,"abstract":"<div><p>Mitochondria are central to cellular energy production and metabolic regulation, particularly in cardiomyocytes. These organelles constantly undergo cycles of fusion and fission, orchestrated by key proteins like Dynamin-related Protein 1 (Drp-1). This review focuses on the intricate roles of Drp-1 in regulating mitochondrial dynamics, its implications in cardiovascular health, and particularly in myocardial infarction. Drp-1 is not merely a mediator of mitochondrial fission; it also plays pivotal roles in autophagy, mitophagy, apoptosis, and necrosis in cardiac cells. This multifaceted functionality is often modulated through various post-translational alterations, and Drp-1′s interaction with intracellular calcium (Ca2 + ) adds another layer of complexity. We also explore the pathological consequences of Drp-1 dysregulation, including increased reactive oxygen species (ROS) production and endothelial dysfunction. Furthermore, this review delves into the potential therapeutic interventions targeting Drp-1 to modulate mitochondrial dynamics and improve cardiovascular outcomes. We highlight recent findings on the interaction between Drp-1 and sirtuin-3 and suggest that understanding this interaction may open new avenues for therapeutically modulating endothelial cells, fibroblasts, and cardiomyocytes. As the cardiovascular system increasingly becomes the focal point of aging and chronic disease research, understanding the nuances of Drp-1′s functionality can lead to innovative therapeutic approaches.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101904"},"PeriodicalIF":4.4,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141033220","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":"Choice of medium affects PBMC quantification, cell size, and downstream respiratory analysis","authors":"Ida Bager Christensen ,&nbsp;Lucas Ribas ,&nbsp;Maria Mosshammer ,&nbsp;Marie-Louise Abrahamsen ,&nbsp;Michael Kühl ,&nbsp;Steen Larsen ,&nbsp;Flemming Dela ,&nbsp;Linn Gillberg","doi":"10.1016/j.mito.2024.101890","DOIUrl":"10.1016/j.mito.2024.101890","url":null,"abstract":"<div><p>High-resolution respirometry (HRR) can assess peripheral blood mononuclear cell (PBMC) bioenergetics, but no standardized medium for PBMC preparation and HRR analysis exist. Here, we study the effect of four different media (MiR05, PBS, RPMI, Plasmax) on the count, size, and HRR (Oxygraph-O2k) of intact PBMCs. Remarkably, the cell count was 21 % higher when PBMCs were resuspended in MiR05 than in PBS or Plasmax, causing O₂ flux underestimation during HRR due to inherent adjustments. Moreover, smaller cell size and cell aggregation was observed in MiR05. Based on our findings, we propose that Plasmax, PBS or RPMI is more suitable than MiR05 for HRR of intact PBMCs. We provide oxygen solubility factors for Plasmax and PBS and encourage further optimization of a standardized HRR protocol for intact PBMCs.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"77 ","pages":"Article 101890"},"PeriodicalIF":4.4,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924000485/pdfft?md5=cd72df97e46171e9279b9d46f78cc07e&pid=1-s2.0-S1567724924000485-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892488","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":"Image-based quantification of mitochondrial iron uptake via Mitoferrin-2","authors":"Marcello Polesel ,&nbsp;Mattheus H.E. Wildschut ,&nbsp;Cédric Doucerain ,&nbsp;Michael Kuhn ,&nbsp;Anna Flace ,&nbsp;Leandro Sá Zanetti ,&nbsp;Anna-Lena Steck ,&nbsp;Maria Wilhelm ,&nbsp;Alvaro Ingles-Prieto ,&nbsp;Tabea Wiedmer ,&nbsp;Giulio Superti-Furga ,&nbsp;Vania Manolova ,&nbsp;Franz Dürrenberger","doi":"10.1016/j.mito.2024.101889","DOIUrl":"10.1016/j.mito.2024.101889","url":null,"abstract":"<div><p>Iron is a trace element that is critical for most living organisms and plays a key role in a wide variety of metabolic processes. In the mitochondrion, iron is involved in producing iron-sulfur clusters and synthesis of heme and kept within physiological ranges by concerted activity of multiple molecules. Mitochondrial iron uptake is mediated by the solute carrier transporters Mitoferrin-1 (SLC25A37) and Mitoferrin-2 (SLC25A28). While Mitoferrin-1 is mainly involved in erythropoiesis, the cellular function of the ubiquitously expressed Mitoferrin-2 remains less well defined. Furthermore, Mitoferrin-2 is associated with several human diseases, including cancer, cardiovascular and metabolic diseases, hence representing a potential therapeutic target. Here, we developed a robust approach to quantify mitochondrial iron uptake mediated by Mitoferrin-2 in living cells. We utilize HEK293 cells with inducible expression of Mitoferrin-2 and measure iron-induced quenching of rhodamine B[(1,10-phenanthroline-5-yl)-aminocarbonyl]benzyl ester (RPA) fluorescence and validate this assay for medium-throughput screening. This assay may allow identification and characterization of Mitoferrin-2 modulators and could enable drug discovery for this target.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101889"},"PeriodicalIF":4.4,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924000473/pdfft?md5=0348899a4579d3f76e860569bddfbb32&pid=1-s2.0-S1567724924000473-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857879","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":"Genomic and non-genomic action of vitamin D on ion channels – Targeting mitochondria","authors":"A.M. Olszewska,&nbsp;M.A. Zmijewski","doi":"10.1016/j.mito.2024.101891","DOIUrl":"10.1016/j.mito.2024.101891","url":null,"abstract":"<div><p>Recent studies revealed that mitochondria are not only a place of vitamin D₃ metabolism but also direct or indirect targets of its activities. This review summarizes current knowledge on the regulation of ion channels from plasma and mitochondrial membranes by the active form of vitamin D₃ (1,25(OH)₂D₃). 1,25(OH)₂D₃, is a naturally occurring hormone with pleiotropic activities; implicated in the modulation of cell differentiation, and proliferation and in the prevention of various diseases, including cancer. Many experimental data indicate that 1,25(OH)₂D₃ deficiency induces ionic remodeling and 1,25(OH)₂D₃ regulates the activity of multiple ion channels. There are two main theories on how 1,25(OH)₂D₃ can modify the function of ion channels. First, describes the involvement of genomic pathways of response to 1,25(OH)₂D₃ in the regulation of the expression of the genes encoding channels, their auxiliary subunits, or additional regulators. Interestingly, intracellular ion channels, like mitochondrial, are encoded by the same genes as plasma membrane channels. Therefore, the comprehensive genomic regulation of the channels from these two different cellular compartments we analyzed using a bioinformatic approach. The second theory explores non-genomic pathways of vitamin D₃ activities. It was shown, that 1,25(OH)₂D₃ indirectly regulates enzymes that impact ion channels, change membrane physical properties, or directly bind to channel proteins. In this article, the involvement of genomic and non-genomic pathways regulated by 1,25(OH)₂D₃ in the modulation of the levels and activity of plasma membrane and mitochondrial ion channels was investigated by an extensive review of the literature and analysis of the transcriptomic data using bioinformatics.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"77 ","pages":"Article 101891"},"PeriodicalIF":4.4,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924000497/pdfft?md5=02b6521a886ce791de1e4b350f243779&pid=1-s2.0-S1567724924000497-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850530","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":"Novel blood and tissue-based mitochondrial D-loop mutations detected in an Iranian NAFLD patient cohort","authors":"Sharareh Kamfar ,&nbsp;Bardia Danaei ,&nbsp;Samane Rahimi ,&nbsp;Vahide Zeinali","doi":"10.1016/j.mito.2024.101888","DOIUrl":"https://doi.org/10.1016/j.mito.2024.101888","url":null,"abstract":"<div><p>Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease characterized by an elusive etiology. In its advanced stages, this condition can pose life-threatening implications. Mitochondrial dysfunction due to its impact on hepatic lipid homeostasis, cytokine release, ROS production, and cell death, contributes to the pathogenesis of NAFLD. Previous research reveals a direct link between NAFLD genetic predictors and mitochondrial dysfunction. The emphasis on the D-loop stems from its association with impaired mtDNA replication, underscoring its crucial role in NAFLD progression. We included 38 Iranian NAFLD patients (comprising 16 patients with non-alcoholic fatty liver [NAFL] and 22 patients with non-alcoholic steatohepatitis [NASH]), with matched blood and liver tissue samples collected from each to compare variations in the mitochondrial D-loop sequence within samples. The mitochondrial DNA (mtDNA) D-loop region was amplified using PCR, and variations were identified through sequencing. The resultant sequences were compared with the reference sequence of human mtDNA available in the MITOMAP Database for comparative analysis. In this study, 97 somatic mutations in the mtDNA D-loop region were identified in NAFLD patients. Our study revealed significant difference between the NAFLD patients and control group in 13 detected mutations (P ≤ 0.05). Novel mutations were discovered in hepatic tissues, while mutation 16220-16221ins C was found in both tissues and blood. A significant difference was found in the distribution of D310 and mt514-mt523 (CA)n repeat variations between NAFLD patients and the control group (P &lt; 0.001). C to T and T to C transitions were the prevalent substitution among patients. Identification of the 16220-16221ins C mutation in both blood and tissue samples from NAFLD patients holds substantial promise as a potential diagnostic marker. However, further research is imperative to corroborate these findings.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"77 ","pages":"Article 101888"},"PeriodicalIF":4.4,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140822803","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 dysfunction, a weakest link of network of aging, relation to innate intramitochondrial immunity of DNA recognition receptors","authors":"Dun-Xian Tan","doi":"10.1016/j.mito.2024.101886","DOIUrl":"https://doi.org/10.1016/j.mito.2024.101886","url":null,"abstract":"<div><p>Aging probably is the most complexed process in biology. It is manifested by a variety of hallmarks. These hallmarks weave a network of aging; however, each hallmark is not uniformly strong for the network. It is the weakest link determining the strengthening of the network of aging, or the maximum lifespan of an organism. Therefore, only improvement of the weakest link has the chance to increase the maximum lifespan but not others. We hypothesize that mitochondrial dysfunction is the weakest link of the network of aging. It may origin from the innate intramitochondrial immunity related to the activities of pathogen DNA recognition receptors. These receptors recognize mtDNA as the PAMP or DAMP to initiate the immune or inflammatory reactions. Evidence has shown that several of these receptors including TLR9, cGAS and IFI16 can be translocated into mitochondria. The potentially intramitochondrial presented pathogen DNA recognition receptors have the capacity to attack the exposed second structures of the mtDNA during its transcriptional or especially the replicational processes, leading to the mtDNA mutation, deletion, heteroplasmy colonization, mitochondrial dysfunction, and alterations of other hallmarks, as well as aging. Pre-consumption of the intramitochondrial presented pathogen DNA recognition receptors by medical interventions including development of mitochondrial targeted small molecule which can neutralize these receptors may retard or even reverse the aging to significantly improve the maximum lifespan of the organisms.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101886"},"PeriodicalIF":4.4,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650501","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":"Telomere length determines the mitochondrial copy number in blastocyst-stage embryos","authors":"Yuki Inoue,&nbsp;Sogo Aoki,&nbsp;Jun Ito,&nbsp;Shunsuke Hara,&nbsp;Komei Shirasuna,&nbsp;Hisataka Iwata","doi":"10.1016/j.mito.2024.101887","DOIUrl":"10.1016/j.mito.2024.101887","url":null,"abstract":"<div><p>Telomere length (TL) and mitochondrial DNA copy number (mt-cn) are associated with embryonic development. Here, we investigated the correlation between TL and mt-cn in bovine embryos to determine whether TL regulates mt-cn.</p><p>TL and mt-cn were closely correlated in embryos derived from six bulls. Treatment of embryos with a telomerase inhibitor (TMPyP) and siTERT shortened the TL and reduced mt-cn in blastocysts. RNA-sequencing of blastocysts developed with TMPyP revealed differentially expressed genes associated with transforming growth factor-β1 signaling and inflammation. In conclusion, TL regulates mt-cn in embryos.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"77 ","pages":"Article 101887"},"PeriodicalIF":4.4,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140787942","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 interplay between hippo signaling and mitochondrial metabolism: Implications for cellular homeostasis and disease","authors":"Priyanka Biswal,&nbsp;Manas Ranjan Sahu,&nbsp;Mir Hilal Ahmad,&nbsp;Amal Chandra Mondal","doi":"10.1016/j.mito.2024.101885","DOIUrl":"https://doi.org/10.1016/j.mito.2024.101885","url":null,"abstract":"<div><p>Mitochondria are the membrane-bound organelles producing energy for cellular metabolic processes. They orchestrate diverse cell signaling cascades regulating cellular homeostasis. This functional versatility may be attributed to their ability to regulate mitochondrial dynamics, biogenesis, and apoptosis. The Hippo pathway, a conserved signaling pathway, regulates various cellular processes, including mitochondrial functions. Through its effectors YAP and TAZ, the Hippo pathway regulates transcription factors and creates a seriatim process that mediates cellular metabolism, mitochondrial dynamics, and survival. Mitochondrial dynamics also potentially regulates Hippo signaling activation, indicating a bidirectional relationship between the two. This review outlines the interplay between the Hippo signaling components and the multifaceted role of mitochondria in cellular homeostasis under physiological and pathological conditions.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101885"},"PeriodicalIF":4.4,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140643973","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 genetic identity of the Vedda: A language isolate of South Asia","authors":"Anjana Welikala ,&nbsp;Shailesh Desai ,&nbsp;Prajjval Pratap Singh ,&nbsp;Amali Fernando ,&nbsp;Kumarasamy Thangaraj ,&nbsp;George van Driem ,&nbsp;Gamini Adikari ,&nbsp;Kamani Tennekoon ,&nbsp;Gyaneshwer Chaubey ,&nbsp;Ruwandi Ranasinghe","doi":"10.1016/j.mito.2024.101884","DOIUrl":"https://doi.org/10.1016/j.mito.2024.101884","url":null,"abstract":"<div><p>Linguistic data from South Asia identified several language isolates in the subcontinent. The Vedda, an indigenous population of Sri Lanka, are the least studied amongst them. Therefore, to understand the initial peopling of Sri Lanka and the genetic affinity of the Vedda with other populations in Eurasia, we extensively studied the high-resolution autosomal and mitogenomes from the Vedda population of Sri Lanka. Our autosomal analyses suggest a close genetic link of Vedda with the tribal populations of India despite no evidence of close linguistic affinity, thus suggesting a deep genetic link of the Vedda with these populations. The mitogenomic analysis supports this association by pointing to an ancient link with Indian populations. We suggest that the Vedda population is a genetically drifted group with limited gene flow from neighbouring Sinhalese and Sri Lankan Tamil populations. Interestingly, the genetic ancestry sharing of Vedda neglects the isolation-by-distance model. Collectively, the demography of Sri Lanka is unique, where Sinhalese and Sri Lankan Tamil populations excessively admixed, whilst Vedda largely preserved their isolation and deep genetic association with India.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101884"},"PeriodicalIF":4.4,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140606827","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 mechanisms in Cerebral Ischemia-Reperfusion Injury: Unravelling the intricacies","authors":"Shiv Kumar Saini ,&nbsp;Damanpreet Singh","doi":"10.1016/j.mito.2024.101883","DOIUrl":"10.1016/j.mito.2024.101883","url":null,"abstract":"<div><p>Cerebral ischemic stroke is a major contributor to physical impairments and premature death worldwide. The available reperfusion therapies for stroke in the form of mechanical thrombectomy and intravenous thrombolysis increase the risk of cerebral ischemia–reperfusion (I-R) injury due to sudden restoration of blood supply to the ischemic region. The injury is manifested by hemorrhagic transformation, worsening of neurological impairments, cerebral edema, and progression to infarction in surviving patients. A complex network of multiple pathological processes has been known to be involved in the pathogenesis of I-R injury. Primarily, 3 major contributors namely oxidative stress, neuroinflammation, and mitochondrial failure have been well studied in I-R injury. A transcription factor, Nrf2 (Nuclear factor erythroid 2-related factor 2) plays a crucial defensive role in resisting the deleterious effects of I-R injury and potentiating the cellular protective mechanisms. In this review, we delve into the critical function of mitochondria and Nrf2 in the context of cerebral I-R injury. We summarized how oxidative stress, neuroinflammation, and mitochondrial anomaly contribute to the pathophysiology of I-R injury and further elaborated the role of Nrf2 as a pivotal guardian of cellular integrity. The review further highlighted Nrf2 as a putative therapeutic target for mitochondrial dysfunction in cerebral I-R injury management.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"77 ","pages":"Article 101883"},"PeriodicalIF":4.4,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140766865","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}