Journal of World Mitochondria Society最新文献_第6页

Perturbation of mitochondrial dynamics in Alcoholic Liver Disease. 酒精性肝病线粒体动力学的扰动。

Journal of World Mitochondria Society Pub Date : 2016-09-14 DOI: 10.18143/JWMS_V2I2_1948

E. Palma, A. Riva, S. Mudan, N. Manyakin, D. Morrison, Christophe Moreno, D. Degré, E. Trépo, P. Sancho-Bru, J. Altamirano, J. Caballería, Gemma Odena, Ramon Battaler, Roger Williams, S. Chokshi

{"title":"Perturbation of mitochondrial dynamics in Alcoholic Liver Disease.","authors":"E. Palma, A. Riva, S. Mudan, N. Manyakin, D. Morrison, Christophe Moreno, D. Degré, E. Trépo, P. Sancho-Bru, J. Altamirano, J. Caballería, Gemma Odena, Ramon Battaler, Roger Williams, S. Chokshi","doi":"10.18143/JWMS_V2I2_1948","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1948","url":null,"abstract":"In Europe alcohol consumption causes 6.5% of deaths and Alcoholic Liver Disease (ALD) is the predominant cause of liver disease[1]. In the pathogenesis of ALD the involvement of mitochondria is well established[2, 3], morphological alterations (megamitochondria) in the liver biopsies of patients are recognised as hallmarks of ALD[4]. However, the impact of alcohol on mitochondrial dynamics and mitochondria-shaping proteins (MSP) remains unknown. The effect of alcohol was investigated in vitro (hepatoma cells), ex vivo (human liver slices) and in 55 patients with ALD. The analysis by confocal/electron microscopy revealed an initial mitochondrial hyper-fragmentation induced by short-term ethanol treatment, preceding cell injury or mitochondrial dysfunction; while megamitochondria developed as a consequence of longer exposure. These structural modifications were associated with changes in the MSP regulating fragmentation but not fusion (gene/protein expression), in particular in Dynamin related protein-1 (Drp-1) and its receptors MiD51 and Mff. When Drp-1 was inactivated, the cells shown abrogation of ethanol-induced hyper-fragmentation and increased megamitochondria formation, suggesting that both phenomena are induced by alcohol via Drp-1. The pivotal role of Drp-1 in ALD was confirmed in liver biopsies of patients with alcoholic hepatitis, opening new perspectives in the development of therapies aimed to modulate its activity.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114438524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Mitochondrial dysfunction and glucose uptake 线粒体功能障碍和葡萄糖摄取

Journal of World Mitochondria Society Pub Date : 2016-09-14 DOI: 10.18143/JWMS_V2I2_1958

W. Koopman

{"title":"Mitochondrial dysfunction and glucose uptake","authors":"W. Koopman","doi":"10.18143/JWMS_V2I2_1958","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1958","url":null,"abstract":"Mitochondria play a central role in cellular energy production and their dysfunction can trigger a compensatory increase in glycolytic flux to sustain cellular ATP levels. Here we studied the mechanism of this homeostatic phenomenon in C2C12 myoblasts. Acute (30 min) mitoenergetic dysfunction induced by the mitochondrial inhibitors piericidin A and antimycin A, stimulated Glut1-mediated glucose uptake without altering Glut1 mRNA or plasma membrane levels. The serine/threonine liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK) played a central role in this stimulation. In contrast, ataxia-telangiectasia mutated (ATM; a potential AMPK kinase), Src (previously highlighted to stimulate Glut1-mediated glucose uptake), and hydroethidium (HEt)-oxidizing reactive oxygen species (ROS; increased in piericidin A- and antimycin A-treated cells), appeared not to be involved in glucose uptake simulation. Inhibitor treatment increased NAD+ and NADH levels (leading to a lower NAD+/NADH ratio), but did not affect the level of Glut1 acetylation. Stimulation of glucose uptake was greatly reduced upon inhibition of Sirt2 or mTOR/RAPTOR. We propose that mitochondrial dysfunction triggers LKB1-mediated AMPK activation, which stimulates Sirt2 phosphorylation, leading to activation of Akt/mTOR/RAPTOR and Glut1-mediated glucose uptake.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"380 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127588150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Browning-inducers modify the differentiation of human adipocytes from different anatomical sites and enhance their mitochondrial respiration 褐化诱导剂可以改变人体脂肪细胞在不同解剖部位的分化，并增强其线粒体呼吸作用

Journal of World Mitochondria Society Pub Date : 2016-09-14 DOI: 10.18143/JWMS_V2I2_1950

E. Kristóf, Quang‐Minh Doan‐Xuan, Ágnes Klusóczki, F. Győry, S. Póliska, Z. Bacsó, P. Bai, L. Fésüs

{"title":"Browning-inducers modify the differentiation of human adipocytes from different anatomical sites and enhance their mitochondrial respiration","authors":"E. Kristóf, Quang‐Minh Doan‐Xuan, Ágnes Klusóczki, F. Győry, S. Póliska, Z. Bacsó, P. Bai, L. Fésüs","doi":"10.18143/JWMS_V2I2_1950","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1950","url":null,"abstract":"Several studies highlighted the strong negative correlation between obesity and active brown adipose tissue amount in adult humans. There are at least two types of thermogenic fat depots, classical brown and beige, which have different origins and tissue distribution [1]. We intended to clarify whether preadipocytes from different anatomical sites are capable of initiating a browning program in parallel with the enhancement of mitochondrial respiration in response to browning-inducers. Preadipocytes obtained from herniotomy (abdominal subcutaneous) or thyroid surgery (“deep neck” and cervical subcutaneous) and a human preadipocyte cell line (SGBS) were differentiated into white, brown (by BMP7 treatment) or beige (by irisin and clozapine administration or by a previously described cocktail) adipocytes. To assess browning, gene expression measurements and laser-scanning cytometry based morphology analysis were performed [2]. Oxygen consumption was measured using an XF96 oxymeter. Differentiating adipocytes treated with browning-inducers had smaller lipid droplets, more mitochondrial DNA, higher mitochondrial respiration and contained more Ucp1 protein than white adipocytes. Browning adipocytes utilize more fatty acids by beta-oxidation and increase their respiration by activating a futile cycle of creatine metabolism [3]. Next, we intend to identify molecular markers to characterize those preadipocytes that are capable to implement an effective browning program.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133234821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial complex I subunits of Candida albicans are coordinators of biological processes both inside and outside of mitochondria 白色念珠菌的线粒体复合体I亚基是线粒体内外生物过程的协调者

Journal of World Mitochondria Society Pub Date : 2016-09-13 DOI: 10.18143/JWMS_V2I2_1932

Xiaodong She, Pengyi Zhang, R. Calderone, Weida Liu, Dongmei Li

{"title":"Mitochondrial complex I subunits of Candida albicans are coordinators of biological processes both inside and outside of mitochondria","authors":"Xiaodong She, Pengyi Zhang, R. Calderone, Weida Liu, Dongmei Li","doi":"10.18143/JWMS_V2I2_1932","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1932","url":null,"abstract":"The mitochondrial ETC complex I (CI) is present in C. albicans and regulation of CI is based on nutrient availability. Our recent studies indicate that NDH51 (a component of the CI core), NUO1 and NUO2 (two fungal specific- CI proteins), and GOA1 (Candida specific- CI protein), are all required for CI integrity. Lack of any of these subunits results in an azole hypersensitivity, avirulence, failure of immunity, and a loss of chronological aging. Genomics and proteomics studies reveal that cell membrane synthesis and wall assembly in this organism are regulated in tandem with CI nDNA genes but not mtDNA-encoded genes. When synthesis of CI subunits, phospholipid and ergosterol are repressed in three CI mutants, proteins for CIV assembly and the alternative oxidase (AOX2) are upgraded. Differential proteins of mutants suggest that NUO1 participates in nucleotide synthesis, ribosomal biogenesis and negatively regulates mitochondrial ribosomal biogenesis. NUO2 plays a redundant but minor role in these cellular processes; however, vesicular trafficking and negatively regulated CI assembly via inhibition of CIA30 are more NUO2–specific. GOA1, on the other hand, appears to regulate membrane transport, to provide protection against mitochondrial ROS and to balance TCA intermediate flow between mitochondria and the cytoplasm.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130780526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial-Targeting Ceria Nanoparticles as a Potential Antioxidant drug for Therapy of Alzheimer’s Disease. 线粒体靶向氧化铈纳米颗粒作为治疗阿尔茨海默病的潜在抗氧化药物

Journal of World Mitochondria Society Pub Date : 2016-09-13 DOI: 10.18143/JWMS_V2I2_1937

Hyek Jin Kwon, M. Cha, Dokyoon Kim, I. Mook-Jung, T. Hyeon

{"title":"Mitochondrial-Targeting Ceria Nanoparticles as a Potential Antioxidant drug for Therapy of Alzheimer’s Disease.","authors":"Hyek Jin Kwon, M. Cha, Dokyoon Kim, I. Mook-Jung, T. Hyeon","doi":"10.18143/JWMS_V2I2_1937","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1937","url":null,"abstract":"Mitochondrial oxidative stress is an important pathologic factor in neurodegenerative diseases, including Alzheimer’s disease. Abnormal production of reactive oxygen species (ROS), resulting from mitochondrial dysfunction, leads to neuronal cell death. Ceria (CeO2) nanoparticles less than 5 nm are known to perform as powerful and recyclable ROS scavengers by exchanging between Ce3+ and Ce4+ oxidation states. Hence, targeting ceria nanoparticles specifically to mitochondria might be a promising therapeutic approach for neurodegenerative diseases. Here, we report the design and synthesis of triphenylphosphonium-conjugated ceria nanoparticles which localize to mitochondria of subicular cells due to their small hydrodynamic diameter (22 nm) and highly positive charge (+45 mV). The triphenylphosphonium-conjugated ceria nanoparticles diminish mitochondrial oxidative stress and suppress neuronal death in a 5XFAD transgenic Alzheimer’s disease mouse model after two months. The triphenylphosphonium-conjugated ceria nanoparticles alleviate reactive gliosis and morphological mitochondria damage observed in these mice. Altogether, our data indicate that the triphenylphosphonium-conjugated ceria nanoparticles are a potential therapeutic candidate for mitochondrial oxidative stress in Alzheimer’s disease.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129054967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GLUCOCORTICOID LONG-TERM TREATMENT INDUCES OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION AND ATROPHY OF SKELETAL MUSCLES 糖皮质激素长期治疗可引起氧化应激、线粒体功能障碍和骨骼肌萎缩

Journal of World Mitochondria Society Pub Date : 2016-09-09 DOI: 10.18143/JWMS_V2I2_1919

E. Balboa, F. Saavedra, T. Regueira, J. Sáez

{"title":"GLUCOCORTICOID LONG-TERM TREATMENT INDUCES OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION AND ATROPHY OF SKELETAL MUSCLES","authors":"E. Balboa, F. Saavedra, T. Regueira, J. Sáez","doi":"10.18143/JWMS_V2I2_1919","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1919","url":null,"abstract":"The mechanism of glucocorticoid-induced atrophy remains unclear. Objectives: to evaluate the involvement of oxidative stress, connexin hemichannels (Cx HCs) and mitochondrial dysfunction in dexamethasone (DEX)-induced muscle atrophy. Methods: We used muscle specific Cx43/Cx45 expression deficient and wild-type mice treated with DEX or DEX+vitaminE. Atrophy was evaluated by atrogin-1 reactivity (immunofluorescense) and cross sectional area (CSA) of myofibers. The functional state of mitochondria was evaluated by measuring oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and mitochondrial superoxide production (mtROS). The Cx expression was evaluated by immunofluorescence. Results: At day 7th of DEX treatment myofibers of wild-type mice showed reduced MMP, increased mtROS, reduced OCR, increased atrogin-1 and reduced CSA.These changes were absent in muscles of wild-type mice treated with DEX + vitaminE and in muscles Cx43/45 expression deficient mice.Moreover, DEX induced de novo expression of Cx43/Cx45 in myofibers of wild-type mice, which was prevented by vitaminE. Conclusions: DEX induces oxidative stress and Cx43/Cx45 de novo expression, which have a negative impact on mitochondrial function leading to muscle atrophy. Consequently, these side effects of chronic glucocorticoid treatment might be avoided by co-administration of antioxidant agents such as vitaminE and a Cx HC blocker.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":" 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"113949562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A TRACKABLE DRUG DELIVERY CARRIER MODIFIED WITH MITOCHONDRIAL TARGETING CONJUGATE FOR OVERCOMING DRUG RESISTANCE 一种线粒体靶向偶联物修饰的可追踪药物递送载体，用于克服耐药性

Journal of World Mitochondria Society Pub Date : 2016-09-09 DOI: 10.18143/JWMS_V2I2_1924

Ye Zhang, Hong Bi

{"title":"A TRACKABLE DRUG DELIVERY CARRIER MODIFIED WITH MITOCHONDRIAL TARGETING CONJUGATE FOR OVERCOMING DRUG RESISTANCE","authors":"Ye Zhang, Hong Bi","doi":"10.18143/JWMS_V2I2_1924","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1924","url":null,"abstract":"Fluorescent carbon quantum dots (CQDs) are considered as a good candidate for bioimaging as well as drug delivery system (DDS) due to their low cytotoxicity and high biocompatibility.1 D-α-tocopheryl polyethylene glycol succinate (TPGS), an inhibitor of P-glycoprotein (P-gp), has been used for developing a variety of TPGS-containing nanomedicines to overcome multidrug resistance (MDR) and enhance treatment efficacy in cancer chemotherapy. 2 In this work, a new DDS is constructed by using triphenylphosphine conjugated TPGS (TPP-TPGS) as a mitochondrial targeting modifier to functionalize oil-soluble CQDs and loading an anticancer drug, doxorubicin (DOX), in the bioconjugates of CQDs-TPGS-TPP. Accordingly, multi-functionalities (water-solubility, mitochondria-targeting, P-gp inhibition capability as well as imaging-trackable drug delivery property) are endowed to the as-formed DDS. Evaluations of cytotoxicity, cell imaging, and mitochondrial targeting were performed on the human breast cancer MCF-7 cell line. The TPP-modified DDS could be more uptaken by cells and preferentially distributed to the mitochondria. In DOX-resistant MCF-7 cells, an enhanced cytotoxicity was observed for the DDS loading with DOX (CQDs-TPGS-DOX-TPP) in comparison to free DOX and non-targeting conjugates (CQDs-TPGS-DOX). This work highlights promising application of the mitochondrial targeted DDS in reversing drug resistance in cancer therapy.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"51 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123094643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vasoactive Intestinal Peptide protects mitochondria against the detrimental effects of TNFα and IFNγ induced during Citrobacter rodentium infection with partial alleviation of colitis 血管活性肠肽保护线粒体免受鼠柠檬酸杆菌感染诱导的TNFα和IFNγ的有害影响，部分缓解结肠炎

Journal of World Mitochondria Society Pub Date : 2016-09-09 DOI: 10.18143/JWMS_V2I2_1917

A. Maiti, S. Lindén

引用次数: 0

THE EXPRESSION OF COENZYME Q-SYNTHESIS GENES CHANGES DURING AGING 随着年龄的增长，辅酶q合成基因的表达发生了变化

Journal of World Mitochondria Society Pub Date : 2016-09-09 DOI: 10.18143/JWMS_V2I2_1927

G. López-Lluch, C. Campos-Silva, Iván Reyes-Torres, Maximiliano Rivera, Catherine Meza-Torres, Elisabet Rodríguez-Bies, P. Navas

{"title":"THE EXPRESSION OF COENZYME Q-SYNTHESIS GENES CHANGES DURING AGING","authors":"G. López-Lluch, C. Campos-Silva, Iván Reyes-Torres, Maximiliano Rivera, Catherine Meza-Torres, Elisabet Rodríguez-Bies, P. Navas","doi":"10.18143/JWMS_V2I2_1927","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1927","url":null,"abstract":"Objectives. Coenzyme Q (Q) is essential in the activity of the electron transport. Its synthesis involves a complex of 10 different proteins. We determine the evolution of the expression of the gene involved in coenzyme Q synthesis along mouse aging. Methodology. The mRNA levels of all the known components of the coenzyme Q-synthesis machinery were analysed in different organs such as muscle, brain, kidney and liver by qPCR from mice aged 8 (young), 18 (mature) and 24 (old) months. Results. Liver showed higher changes in mRNA levels of the different components. The mRNA levels of the different components of the complex of synthesis of Q were higher in mature animals in comparison with young and old animals. When mRNAs of young and old animals were compared, only a minor decrease was found. A similar behaviour was found in kidney. In brain and muscle, changes were minor although most of the changes showed a similar pattern than in liver. Conclusions. Our results indicate that age is an important factor affecting COQ gene expression. Age influence depends on the organ studied. In general, organs from mature animals show higher levels of CoQ-gene mRNA than young and old animals.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129727160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic dysfunction of the mitochondrial respiratory chain impairs proteasome activity 线粒体呼吸链的遗传功能障碍损害蛋白酶体活性

Journal of World Mitochondria Society Pub Date : 2016-09-09 DOI: 10.18143/JWMS_V2I2_1934

K. Berschneider, Laura S. Kremer, Alexandra Kukat, Jennifer Wettmarshausen, Christine von Törne, S. Hauck, A. Geerlof, Fabiana Perocci, A. Trifunovic, O. Eickelberg, H. Prokisch, S. Meiners

{"title":"Genetic dysfunction of the mitochondrial respiratory chain impairs proteasome activity","authors":"K. Berschneider, Laura S. Kremer, Alexandra Kukat, Jennifer Wettmarshausen, Christine von Törne, S. Hauck, A. Geerlof, Fabiana Perocci, A. Trifunovic, O. Eickelberg, H. Prokisch, S. Meiners","doi":"10.18143/JWMS_V2I2_1934","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1934","url":null,"abstract":"Background: Mitochondria are the central energy producers and signaling platforms of the cell. Recent evidence links mitochondrial function to the main protein degradation machinery of the cell – the ubiquitin proteasome system. Pharmacological inhibition of mitochondrial respiratory chain results in reduced ATP production and excessive formation of reactive oxygen species (ROS) which both impair proteasome function [1]. Objective: We here analyzed the ROS-independent effect of impaired oxidative phosphorylation on proteasome function. Methodology and results: We used embryonic fibroblast from mutator mice that accumulate mutations in mitochondrial DNA resulting in loss of mitochondrial respiration [2] as well as human skin fibroblasts from patients with mitochondrial complex I mutations and comprehensively analyzed expression and activity of cellular proteasome complexes. Mutations in the mitochondrial DNA caused respiratory chain dysfunction and resulted in diminished assembly and activity of 26S and PA28γ-associated proteasome complexes [3] in mutator cells. Dampening of the proteasome activity was independent of excessive ROS production and ATP supply and made them less sensitive towards proteasome inhibition. Conclusion: Disturbed proteasomal function may represent a confounding factor for progression of severe hereditary mitochondrial respiratory chain disorders.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"209 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132676659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0