Post-translational Modifications of Key Machinery in the Control of Mitophagy. Issue 1 (January 2020)

• Record Type: Journal Article
• Authors: Wang, Liming; Qi, Hao; Tang, Yancheng; Shen, Han-Ming
• Is Part Of: Trends in biochemical sciences. Volume 45:Issue 1(2020)
• Page Start: 58
• Page End: 75
• Publication Date: 2020-01
• Subjects: autophagy -- mitophagy -- PTMs -- PINK1 -- Parkin -- ubiquitin; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2019.08.002
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : 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. Highlights: Five main PTMs (phosphorylation, ubiquitination, acetylation, glycosylation, SUMOylation) as well as their respective reverse processes are involved in the regulation of mitophagy. Three kinases (PINK1, TBK1, and ULK1) mediate three amplification loops in the control of mitophagy. Crosstalk among the different forms of PTM determines the course of mitophagy. Targeting the PTMs of key mitophagy effectors offers opportunities for the development of novel interventional strategies for mitophagy and related diseases.