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衰老与长寿中的线粒体自噬

Mitophagy in aging and longevity.

作者信息

Guo Jing, Chiang Wei-Chung

机构信息

Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan.

出版信息

IUBMB Life. 2022 Apr;74(4):296-316. doi: 10.1002/iub.2585. Epub 2021 Dec 10.

Abstract

The clearance of damaged or unwanted mitochondria by autophagy (also known as mitophagy) is a mitochondrial quality control mechanism postulated to play an essential role in cellular homeostasis, metabolism, and development and confers protection against a wide range of diseases. Proper removal of damaged or unwanted mitochondria is essential for organismal health. Defects in mitophagy are associated with Parkinson's, Alzheimer's disease, cancer, and other degenerative disorders. Mitochondria regulate organismal fitness and longevity via multiple pathways, including cellular senescence, stem cell function, inflammation, mitochondrial unfolded protein response (mtUPR), and bioenergetics. Thus, mitophagy is postulated to be pivotal for maintaining organismal healthspan and lifespan and the protection against aged-related degeneration. In this review, we will summarize recent understanding of the mechanism of mitophagy and aspects of mitochondrial functions. We will focus on mitochondria-related cellular processes that are linked to aging and examine current genetic evidence that supports the hypothesis that mitophagy is a pro-longevity mechanism.

摘要

通过自噬(也称为线粒体自噬)清除受损或不需要的线粒体是一种线粒体质量控制机制,据推测在细胞稳态、新陈代谢和发育中起重要作用,并能预防多种疾病。正确清除受损或不需要的线粒体对机体健康至关重要。线粒体自噬缺陷与帕金森病、阿尔茨海默病、癌症和其他退行性疾病有关。线粒体通过多种途径调节机体适应性和寿命,包括细胞衰老、干细胞功能、炎症、线粒体未折叠蛋白反应(mtUPR)和生物能量学。因此,线粒体自噬被认为对维持机体健康期和寿命以及预防与衰老相关的退化至关重要。在这篇综述中,我们将总结对线粒体自噬机制和线粒体功能方面的最新认识。我们将关注与衰老相关的线粒体相关细胞过程,并研究支持线粒体自噬是一种促进长寿机制这一假说的当前遗传学证据。

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