Mitochondrion最新文献

{"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}

{"title":"Deficiency of the BKCa potassium channel displayed significant implications for the physiology of the human bronchial epithelium","authors":"Kamila Maliszewska-Olejniczak ,&nbsp;Karolina Pytlak ,&nbsp;Adrianna Dabrowska ,&nbsp;Monika Zochowska ,&nbsp;Jakub Hoser ,&nbsp;Agnieszka Lukasiak ,&nbsp;Miroslaw Zajac ,&nbsp;Bogusz Kulawiak ,&nbsp;Piotr Bednarczyk","doi":"10.1016/j.mito.2024.101880","DOIUrl":"https://doi.org/10.1016/j.mito.2024.101880","url":null,"abstract":"<div><p>Plasma membrane large-conductance calcium-activated potassium (BK_Ca) channels are important players in various physiological processes, including those mediated by epithelia. Like other cell types, human bronchial epithelial (HBE) cells also express BK_Ca in the inner mitochondrial membrane (mitoBK_Ca). The genetic relationships between these mitochondrial and plasma membrane channels and the precise role of mitoBK_Ca in epithelium physiology are still unclear. Here, we tested the hypothesis that the mitoBK_Ca channel is encoded by the same gene as the plasma membrane BK_Ca channel in HBE cells. We also examined the impact of channel loss on the basic function of HBE cells, which is to create a tight barrier. For this purpose, we used CRISPR/Cas9 technology in 16HBE14o- cells to disrupt the <em>KCNMA1</em> gene, which encodes the α-subunit responsible for forming the pore of the plasma membrane BK_Ca channel. Electrophysiological experiments demonstrated that the disruption of the <em>KCNMA1</em> gene resulted in the loss of BK_Ca-type channels in the plasma membrane and mitochondria. We have also shown that HBE ΔαBK_Ca cells exhibited a significant decrease in transepithelial electrical resistance which indicates a loss of tightness of the barrier created by these cells. We have also observed a decrease in mitochondrial respiration, which indicates a significant impairment of these organelles.</p><p>In conclusion, our findings indicate that a single gene encodes both populations of the channel in HBE cells. Furthermore, this channel is critical for maintaining the proper function of epithelial cells as a cellular barrier.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101880"},"PeriodicalIF":4.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924000382/pdfft?md5=02282cf61659e8ea6d1e1589b4392c02&pid=1-s2.0-S1567724924000382-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140551141","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 Schizosaccharomyces pombe DEAD-box protein Mss116 is required for mitoribosome assembly and mitochondrial translation","authors":"Yirong Wang,&nbsp;Gang Feng,&nbsp;Ying Huang","doi":"10.1016/j.mito.2024.101881","DOIUrl":"https://doi.org/10.1016/j.mito.2024.101881","url":null,"abstract":"<div><p>DEAD-box helicases are important players in mitochondrial gene expression, which is necessary for mitochondrial respiration. In this study, we characterized <em>Schizosaccharomyces pombe</em> Mss116 (spMss116), a member of the family of DEAD-box RNA helicases. Deletion of <em>spmss116</em> in a mitochondrial intron-containing background significantly reduced the levels of mitochondrial DNA (mtDNA)-encoded <em>cox1</em> and <em>cob1</em> mRNAs and impaired mitochondrial translation, leading to a severe respiratory defect and a loss of cell viability during stationary phase. Deletion of mitochondrial introns restored the levels of <em>cox1</em> and <em>cob1</em> mRNAs to wide-type (WT) levels but could not restore mitochondrial translation and respiration in Δ<em>spmss116</em> cells. Furthermore, deletion of <em>spmss116</em> in both mitochondrial intron-containing and intronless backgrounds impaired mitoribosome assembly and destabilization of mitoribosomal proteins. Our findings suggest that defective mitochondrial translation caused by deletion of <em>spmss116</em> is most likely due to impaired mitoribosome assembly.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101881"},"PeriodicalIF":4.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546057","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":"Machine learning-based 3D segmentation of mitochondria in polarized epithelial cells","authors":"Nan W. Hultgren ,&nbsp;Tianli Zhou ,&nbsp;David S. Williams","doi":"10.1016/j.mito.2024.101882","DOIUrl":"https://doi.org/10.1016/j.mito.2024.101882","url":null,"abstract":"<div><p>Mitochondria are dynamic organelles that alter their morphological characteristics in response to functional needs. Therefore, mitochondrial morphology is an important indicator of mitochondrial function and cellular health. Reliable segmentation of mitochondrial networks in microscopy images is a crucial initial step for further quantitative evaluation of their morphology. However, 3D mitochondrial segmentation, especially in cells with complex network morphology, such as in highly polarized cells, remains challenging. To improve the quality of 3D segmentation of mitochondria in super-resolution microscopy images, we took a machine learning approach, using 3D Trainable Weka, an ImageJ plugin. We demonstrated that, compared with other commonly used methods, our approach segmented mitochondrial networks effectively, with improved accuracy in different polarized epithelial cell models, including differentiated human retinal pigment epithelial (RPE) cells. Furthermore, using several tools for quantitative analysis following segmentation, we revealed mitochondrial fragmentation in bafilomycin-treated RPE cells.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101882"},"PeriodicalIF":4.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637880","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":"Remarkable clinical improvement with oral nucleoside treatment in a patient with adult-onset TK2 deficiency: A case report","authors":"Laura Bermejo-Guerrero ,&nbsp;Ana Hernández-Voth ,&nbsp;Pablo Serrano-Lorenzo ,&nbsp;Alberto Blázquez ,&nbsp;Paloma Martin-Jimenez ,&nbsp;Miguel A. Martin ,&nbsp;Cristina Domínguez-González","doi":"10.1016/j.mito.2024.101879","DOIUrl":"https://doi.org/10.1016/j.mito.2024.101879","url":null,"abstract":"<div><h3>Objectives</h3><p>Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms. We present the response to treatment in a patient with adult-onset TK2d.</p></div><div><h3>Methods</h3><p>An adult with ptosis, ophthalmoplegia, facial, neck, and proximal muscle weakness, non-invasive nocturnal mechanical ventilation, and dysphagia due to biallelic pathogenic variants in <em>TK2</em> received treatment with 260 mg/kg/day of deoxycytidine (dC) and deoxythymidine (dT) under a Compassionate Use Program. Prospective motor and respiratory assessments are presented.</p></div><div><h3>Results</h3><p>After 27 months of follow-up, the North Star Ambulatory Assessment improved by 11 points, he walked 195 m more in the 6 Minute-Walking-Test, ran 10 s faster in the 100-meter time velocity test, and the Forced Vital Capacity stabilized. Growth Differentiation Factor-15 (GDF15) levels, a biomarker of respiratory chain dysfunction, normalized. The only reported side effect was dose-dependent diarrhea.</p></div><div><h3>Discussion</h3><p>Treatment with dC and dT can significantly improve motor performance and stabilize respiratory function safely in patients with adult-onset TK2d.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101879"},"PeriodicalIF":4.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924000370/pdfft?md5=f6065cc545a49fe4232ad8b4b4438356&pid=1-s2.0-S1567724924000370-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140543630","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":"Role of Rmd9p in 3′-end processing of mitochondrial 15S rRNA in Saccharomyces cerevisiae","authors":"Jitendra Singh ,&nbsp;Sudhir Singh ,&nbsp;Elhassan Ali Fathi Emam ,&nbsp;Umesh Varshney","doi":"10.1016/j.mito.2024.101876","DOIUrl":"https://doi.org/10.1016/j.mito.2024.101876","url":null,"abstract":"<div><p>Ribosome biogenesis, involving processing/assembly of rRNAs and r-proteins is a vital process. In <em>Saccharomyces cerevisiae</em> mitochondria, ribosomal small subunit comprises 15S rRNA (15S). While the 15S 5′-end processing uses Ccm1p and Pet127p, the mechanisms of the 3′-end processing remain unclear. We reveal involvement of Rmd9p in safeguarding/processing 15S 3′-end. Rmd9p deficiency results in a cleavage at a position 183 nucleotides upstream of 15S 3′-end, and in the loss of the 3′-minor domain. Rmd9p binds to the sequences in the 3'-end region of 15S, and a genetic interaction between <em>rmd9</em> and <em>dss1</em> indicates that Rmd9p regulates/limits mtEXO activity during the 3′-end spacer processing.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101876"},"PeriodicalIF":4.4,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140552224","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":"Mrs2-mediated mitochondrial magnesium uptake is essential for the regulation of MCU-mediated mitochondrial Ca2+ uptake and viability","authors":"Thiruvelselvan Ponnusamy,&nbsp;Prema Velusamy,&nbsp;Santhanam Shanmughapriya","doi":"10.1016/j.mito.2024.101877","DOIUrl":"10.1016/j.mito.2024.101877","url":null,"abstract":"<div><p>Mitochondrial Ca²⁺ uptake is essential in regulating bioenergetics, cell death, and cytosolic Ca²⁺ transients. Mitochondrial Calcium Uniporter (MCU) mediates the mitochondrial Ca²⁺ uptake. Though MCU regulation by MICUs is unequivocally established, there needs to be more knowledge of whether divalent cations regulate MCU. Here, we set out to understand the mitochondrial matrix Mg²⁺-dependent regulation of MCU activity. We showed that decreased matrix [Mg²⁺] is associated with increased MCU activity and significantly prompted mitochondrial permeability transition pore opening. Our findings support the critical role of mMg²⁺ in regulating MCU activity.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101877"},"PeriodicalIF":4.4,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140769285","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 sodium/glucose cotransporter type 2 and mitochondrial ionic environment","authors":"Gianmarco Borriello ,&nbsp;Veronica Buonincontri ,&nbsp;Antonio de Donato ,&nbsp;Michele Della Corte ,&nbsp;Ilenia Gravina ,&nbsp;Pietro Iulianiello ,&nbsp;Rashmi Joshi ,&nbsp;Pasquale Mone ,&nbsp;Giovanna Cacciola ,&nbsp;Davide Viggiano","doi":"10.1016/j.mito.2024.101878","DOIUrl":"https://doi.org/10.1016/j.mito.2024.101878","url":null,"abstract":"<div><p>Mitochondrial volume is maintained through the permeability of the inner mitochondrial membrane by a specific aquaporin and the osmotic balance between the mitochondrial matrix and cellular cytoplasm. Various electrolytes, such as calcium and hydrogen ions, potassium, and sodium, as well as other osmotic substances, affect the swelling of mitochondria. Intracellular glucose levels may also affect mitochondrial swelling, although the relationship between mitochondrial ion homeostasis and intracellular glucose is poorly understood. This article reviews what is currently known about how the Sodium-Glucose transporter (SGLT) may impact mitochondrial sodium (Na+) homeostasis. SGLTs regulate intracellular glucose and sodium levels and, therefore, interfere with mitochondrial ion homeostasis because mitochondrial Na+ is closely linked to cytoplasmic calcium and sodium dynamics. Recently, a large amount of data has been available on the effects of SGLT2 inhibitors on mitochondria in different cell types, including renal proximal tubule cells, endothelial cells, mesangial cells, podocytes, neuronal cells, and cardiac cells. The current evidence suggests that SGLT inhibitors (SGLTi) may affect mitochondrial dynamics regarding intracellular Sodium and hydrogen ions. Although the regulation of mitochondrial ion channels by SGLTs is still in its infancy, the evidence accumulated thus far of the effect of SGLTi on mitochondrial functions certainly will foster further research in this direction.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101878"},"PeriodicalIF":4.4,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140543629","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":"Interplay of mitochondria-associated membrane proteins and autophagy: Implications in neurodegeneration","authors":"Prakash G. Kulkarni ,&nbsp;Vaibhavi M. Mohire ,&nbsp;Pranjal P. Waghmare ,&nbsp;Tanushree Banerjee","doi":"10.1016/j.mito.2024.101874","DOIUrl":"10.1016/j.mito.2024.101874","url":null,"abstract":"<div><p>Since the discovery of membrane contact sites between ER and mitochondria called mitochondria-associated membranes (MAMs), several pieces of evidence identified their role in the regulation of different cellular processes such as Ca²⁺ signalling, mitochondrial transport, and dynamics, ER stress, inflammation, glucose homeostasis, and autophagy. The integrity of these membranes was found to be essential for the maintenance of these cellular functions. Accumulating pieces of evidence suggest that MAMs serve as a platform for autophagosome formation. However, the alteration within MAMs structure is associated with the progression of neurodegenerative diseases. Dysregulated autophagy is a hallmark of neurodegeneration. Here, in this review, we highlight the present knowledge on MAMs, their structural composition, and their roles in different cellular functions. We also discuss the association of MAMs proteins with impaired autophagy and their involvement in the progression of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"76 ","pages":"Article 101874"},"PeriodicalIF":4.4,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184854","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}