Atg4 proteolytic activity can be inhibited by Atg1 phosphorylation

Nat Commun. 2017 Aug 18;8(1):295. doi: 10.1038/s41467-017-00302-3.


The biogenesis of autophagosomes depends on the conjugation of Atg8-like proteins with phosphatidylethanolamine. Atg8 processing by the cysteine protease Atg4 is required for its covalent linkage to phosphatidylethanolamine, but it is also necessary for Atg8 deconjugation from this lipid to release it from membranes. How these two cleavage steps are coordinated is unknown. Here we show that phosphorylation by Atg1 inhibits Atg4 function, an event that appears to exclusively occur at the site of autophagosome biogenesis. These results are consistent with a model where the Atg8-phosphatidylethanolamine pool essential for autophagosome formation is protected at least in part by Atg4 phosphorylation by Atg1 while newly synthesized cytoplasmic Atg8 remains susceptible to constitutive Atg4 processing.The protease Atg4 mediates Atg8 lipidation, required for autophagosome biogenesis, but also triggers Atg8 release from the membranes, however is unclear how these steps are coordinated. Here the authors show that phosphorylation by Atg1 inhibits Atg4 at autophagosome formation sites.

Publication types

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

MeSH terms

  • Autophagosomes / metabolism
  • Autophagosomes / ultrastructure
  • Autophagy
  • Autophagy-Related Protein 8 Family / genetics
  • Autophagy-Related Protein 8 Family / metabolism
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism*
  • Blotting, Western
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Phosphatidylethanolamines / metabolism
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Proteolysis
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • ATG8 protein, S cerevisiae
  • Atg4 protein, S cerevisiae
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Microtubule-Associated Proteins
  • Phosphatidylethanolamines
  • Saccharomyces cerevisiae Proteins
  • phosphatidylethanolamine
  • Protein Kinases
  • ATG1 protein, S cerevisiae