Contribution of Atg1-dependent autophagy to TOR-mediated cell growth and survival

Autophagy. 2007 Sep-Oct;3(5):477-9. doi: 10.4161/auto.4348. Epub 2007 Apr 26.

Abstract

The Ser/Thr kinase Atg1 (Ulk1/Unc51) appears to act as a convergence point for multiple signals that regulate autophagy, and in turn interacts with a large number of autophagy-related (Atg) proteins. Working in the Drosophila system, we recently found that overexpression of Atg1 is sufficient to induce autophagy, independent of upstream nutrient signals. We exploited this finding to examine the roles of autophagy in cell growth and death, and to test the interaction of Atg1 with the TOR signaling pathway. These studies provided genetic evidence that autophagy is a potent inhibitor of cell growth, and that high levels of autophagy lead to caspase-dependent apoptotic cell death in vivo. Atg1 also has an inhibitory effect on TOR signaling, indicating the existence of a positive feedback mechanism that may amplify the nutrient-dependent signals that control autophagy.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Autophagy / physiology*
  • Autophagy-Related Protein-1 Homolog
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Gene Expression
  • Genes, Insect
  • Models, Biological
  • Mutation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology*
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Receptor Protein-Tyrosine Kinases
  • tor protein, Drosophila
  • Atg1 protein, Drosophila
  • Autophagy-Related Protein-1 Homolog
  • Protein Serine-Threonine Kinases