Tor directly controls the Atg1 kinase complex to regulate autophagy

Mol Cell Biol. 2010 Feb;30(4):1049-58. doi: 10.1128/MCB.01344-09. Epub 2009 Dec 7.

Abstract

Autophagy is a bulk proteolytic process that is indispensable for cell survival during starvation. Autophagy is induced by nutrient deprivation via inactivation of the rapamycin-sensitive Tor complex1 (TORC1), a protein kinase complex regulating cell growth in response to nutrient conditions. However, the mechanism by which TORC1 controls autophagy and the direct target of TORC1 activity remain unclear. Atg13 is an essential regulatory component of autophagy upstream of the Atg1 kinase complex, and here we show that yeast TORC1 directly phosphorylates Atg13 at multiple Ser residues. Additionally, expression of an unphosphorylatable Atg13 mutant bypasses the TORC1 pathway to induce autophagy through activation of Atg1 in cells growing under nutrient-rich conditions. Our findings suggest that the direct control of the Atg1 complex by TORC1 induces autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Autophagy*
  • Autophagy-Related Proteins
  • Microscopy, Electron
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Autophagy-Related Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • ATG1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • target of rapamycin protein, S cerevisiae