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

Authors :
Xinyu Bai
Yan Wang
Limeng Dai
Yaowen Wang
Wei Pan
Qin Wu
Hong Zhou
Yuehui Yin
Source :
Cell Death Discovery, Vol 7, Iss 1, Pp 1-10 (2021), Cell Death Discovery
Publication Year :
2021
Publisher :
Nature Publishing Group, 2021.

Abstract

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.

Details

Language :
English
ISSN :
20587716
Volume :
7
Issue :
1
Database :
OpenAIRE
Journal :
Cell Death Discovery
Accession number :
edsair.doi.dedup.....4a894259e4f072df17cb7338c4861d53