Deubiquitinating enzyme USP30 negatively regulates mitophagy and accelerates myocardial cell senescence through antagonism of Parkin

作者全名："Pan, Wei; Wang, Yaowen; Bai, Xinyu; Yin, Yuehui; Dai, Limeng; Zhou, Hong; Wu, Qin; Wang, Yan"

作者地址："[Pan, Wei; Bai, Xinyu; Zhou, Hong; Wu, Qin; Wang, Yan] Zunyi Med Univ, Minist Educ, Key Lab Basic Pharmacol, Zunyi 563000, Guizhou, Peoples R China; [Pan, Wei; Bai, Xinyu; Zhou, Hong; Wu, Qin; Wang, Yan] Zunyi Med Univ, Minist Educ, Joint Int Res Lab Ethnomed, Zunyi 563000, Guizhou, Peoples R China; [Pan, Wei; Wang, Yaowen; Yin, Yuehui] Chongqing Med Univ, Affiliated Hosp 2, Dept Cardiol, Chongqing 400010, Peoples R China; [Dai, Limeng] Third Mil Med Univ, Army Med Univ, Coll Basic Med Sci, Dept Med Genet, Chongqing 400038, Peoples R China"

通信作者："Wu, Q; Wang, Y (corresponding author), Zunyi Med Univ, Minist Educ, Key Lab Basic Pharmacol, Zunyi 563000, Guizhou, Peoples R China.; Wu, Q; Wang, Y (corresponding author), Zunyi Med Univ, Minist Educ, Joint Int Res Lab Ethnomed, Zunyi 563000, Guizhou, Peoples R China."

来源：CELL DEATH DISCOVERY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000677614000001

JCR分区：Q2

影响因子：7

年份：2021

卷号：7

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Cell senescence is associated with age-related pathological changes. Increasing evidence has revealed that mitophagy can selectively remove dysfunctional mitochondria. Overexpression of ubiquitin-specific protease 30 (USP30) has been documented to influence mitophagy and deubiquitination of mitochondrial Parkin substrates. This study was conducted to evaluate the roles of USP30 and Parkin in myocardial cell senescence and mitophagy. Initially, myocardial cells were isolated from neonatal SD rats and subjected to d-gal treatment to induce cell senescence, after which the effects of d-gal on mitochondria damage, ROS production, cell senescence, and mitophagy were assessed. The myocardial cells were infected with lentiviruses bearing overexpression plasmids or shRNA targeting Parkin or USP30 to elucidate the effects of Parkin and USP30 on d-gal-induced mitophagy damage and cell senescence. Finally, aging was induced in rats by subcutaneous injection of d-gal to determine the role of Parkin and USP30 on cell senescence in vivo. d-gal was found to trigger mitochondria damage, ROS production, and cell senescence in myocardial cells. The overexpression of Parkin or silencing of USP30 reduced d-gal-induced mitochondrial damage and relieved d-gal-induced myocardial cell senescence. Moreover, the in vivo experiments validated that either elevation of Parkin or silencing USP30 could alleviate d-gal-induced myocardial cell senescence in rats. Silencing USP30 alleviates d-gal-induced mitochondrial damage and consequently suppresses myocardial cell senescence by activating Parkin. Our study highlights the potential of USP30 as a novel target against myocardial cell senescence."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81860643]; Guizhou Provincial Science and Technology Department Social Development Project, China [2009-3074]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (No. 81860643) and Guizhou Provincial Science and Technology Department Social Development Project, China (No. 2009-3074)."