Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila

Cell. 2007 Dec 14;131(6):1137-48. doi: 10.1016/j.cell.2007.10.048.

Abstract

Autophagy is a catabolic process that is negatively regulated by growth and has been implicated in cell death. We find that autophagy is induced following growth arrest and precedes developmental autophagic cell death of Drosophila salivary glands. Maintaining growth by expression of either activated Ras or positive regulators of the class I phosphoinositide 3-kinase (PI3K) pathway inhibits autophagy and blocks salivary gland cell degradation. Developmental degradation of salivary glands is also inhibited in autophagy gene (atg) mutants. Caspases are active in PI3K-expressing and atg mutant salivary glands, and combined inhibition of both autophagy and caspases increases suppression of gland degradation. Further, induction of autophagy is sufficient to induce premature cell death in a caspase-independent manner. Our results provide in vivo evidence that growth arrest, autophagy, and atg genes are required for physiological autophagic cell death and that multiple degradation pathways cooperate in the efficient clearance of cells during development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Protein-1 Homolog
  • Caspases / metabolism
  • Cell Death*
  • Cell Division
  • Drosophila
  • Drosophila Proteins / genetics*
  • Mutation
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Serine-Threonine Kinases / genetics*
  • Salivary Glands / cytology*
  • Salivary Glands / physiology
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Phosphatidylinositol 3-Kinases
  • Atg1 protein, Drosophila
  • Autophagy-Related Protein-1 Homolog
  • Protein-Serine-Threonine Kinases
  • Caspases