Function and molecular mechanism of acetylation in autophagy regulation

Science. 2012 Apr 27;336(6080):474-7. doi: 10.1126/science.1216990.

Abstract

Protein acetylation emerged as a key regulatory mechanism for many cellular processes. We used genetic analysis of Saccharomyces cerevisiae to identify Esa1 as a histone acetyltransferase required for autophagy. We further identified the autophagy signaling component Atg3 as a substrate for Esa1. Specifically, acetylation of K19 and K48 of Atg3 regulated autophagy by controlling Atg3 and Atg8 interaction and lipidation of Atg8. Starvation induced transient K19-K48 acetylation through spatial and temporal regulation of the localization of acetylase Esa1 and the deacetylase Rpd3 on pre-autophagosomal structures (PASs) and their interaction with Atg3. Attenuation of K19-K48 acetylation was associated with attenuation of autophagy. Increased K19-K48 acetylation after deletion of the deacetylase Rpd3 caused increased autophagy. Thus, protein acetylation contributes to control of autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Autophagy*
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Carbohydrate Epimerases / genetics
  • Carbohydrate Epimerases / metabolism
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Mutation
  • Phagosomes / metabolism
  • Protein Processing, Post-Translational
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin-Conjugating Enzymes / chemistry
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism*

Substances

  • ATG8 protein, S cerevisiae
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Microtubule-Associated Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Esa1 protein, S cerevisiae
  • Histone Acetyltransferases
  • Ubiquitin-Conjugating Enzymes
  • RPD3 protein, S cerevisiae
  • Histone Deacetylases
  • Carbohydrate Epimerases
  • L-ribulosephosphate 4-epimerase
  • ATG3 protein, S cerevisiae