Gadd34 induces autophagy through the suppression of the mTOR pathway during starvation

Biochem Biophys Res Commun. 2011 Apr 22;407(4):692-8. doi: 10.1016/j.bbrc.2011.03.077. Epub 2011 Mar 23.

Abstract

Several types of cellular stress induce expression of growth arrest and DNA damage protein 34 (Gadd34). Autophagy occurs under both basal conditions and conditions of stress, such as starvation. Gadd34 and autophagy are both induced under starvation conditions. In this study we found that starvation induced the expression of Gadd34, reduced mTOR activity, and induced autophagy in wild type mice, but not Gadd34 KO mice. Gadd34 bound to and dephosphorylated pTSC2 at Thr1462. Dephosphorylation of TSC2 during the starvation time period leads to the suppression of mTOR, which is a potent inhibitor of autophagy. We concluded that starvation-induced Gadd34 suppresses mTOR and, thereby, induces autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / deficiency
  • Animals
  • Autophagy*
  • Cell Hypoxia
  • Fasting / metabolism*
  • Female
  • Fluorescent Antibody Technique
  • Glucose / deficiency
  • Liver / metabolism
  • Liver / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Protein Phosphatase 1 / genetics
  • Protein Phosphatase 1 / metabolism*
  • Stress, Physiological*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Amino Acids
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Ppp1r15a protein, mouse
  • Protein Phosphatase 1
  • Glucose