Post-translational Modifications of Key Machinery in the Control of Mitophagy

Trends Biochem Sci. 2020 Jan;45(1):58-75. doi: 10.1016/j.tibs.2019.08.002. Epub 2019 Oct 9.

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.

Keywords: PINK1; PTMs; Parkin; autophagy; mitophagy; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Disease
  • Humans
  • Mitochondria / metabolism*
  • Mitophagy*
  • Protein Processing, Post-Translational*