Wang Liming, Qi Hao, Tang Yancheng, Shen Han-Ming
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China.
Trends Biochem Sci. 2020 Jan;45(1):58-75. doi: 10.1016/j.tibs.2019.08.002. Epub 2019 Oct 9.
Mitophagy refers to the process of selective removal of damaged or superfluous mitochondria via the autophagy/lysosome pathway. In the past decade the molecular mechanisms underlying mitophagy have been extensively studied. It is now well established that the key mitophagy machinery undergoes extensive post-translational modifications (PTMs) such as phosphorylation/dephosphorylation, ubiquitination/deubiquitination, and acetylation/deacetylation that involve an array of enzymes including protein kinases/phosphatases, E3 ligases/deubiquitinases, acetyltransferases/deacetylases. In this review we provide a systematic summary of these key PTMs, and discuss the effectors and the functional implications of such PTMs in mitophagy-related diseases. Understanding PTM of the mitophagy machinery offers a unique window of opportunity for the discovery of novel mitophagy interventional strategies and for the control of mitophagy-related diseases.
线粒体自噬是指通过自噬/溶酶体途径选择性清除受损或多余线粒体的过程。在过去十年中,对线粒体自噬的分子机制进行了广泛研究。目前已经明确,关键的线粒体自噬机制会经历广泛的翻译后修饰(PTM),如磷酸化/去磷酸化、泛素化/去泛素化以及乙酰化/去乙酰化,这些修饰涉及一系列酶,包括蛋白激酶/磷酸酶、E3连接酶/去泛素酶、乙酰转移酶/去乙酰化酶。在本综述中,我们对这些关键的PTM进行了系统总结,并讨论了这些PTM在与线粒体自噬相关疾病中的效应器及其功能意义。了解线粒体自噬机制的PTM为发现新的线粒体自噬干预策略以及控制与线粒体自噬相关疾病提供了独特的机会窗口。