Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity

J Cell Biol. 2013 Oct 28;203(2):299-313. doi: 10.1083/jcb.201304123.

Abstract

Autophagy is a conserved eukaryotic process of protein and organelle self-degradation within the vacuole/lysosome. Autophagy is characterized by the formation of an autophagosome, for which Vps34-dervied phosphatidylinositol 3-phosphate (PI3P) is essential. In yeast, Vps34 forms two distinct protein complexes: complex I, which functions in autophagy, and complex II, which is involved in protein sorting to the vacuole. Here we identify and characterize Atg38 as a stably associated subunit of complex I. In atg38Δ cells, autophagic activity was significantly reduced and PI3-kinase complex I dissociated into the Vps15-Vps34 and Atg14-Vps30 subcomplexes. We find that Atg38 physically interacted with Atg14 and Vps34 via its N terminus. Further biochemical analyses revealed that Atg38 homodimerizes through its C terminus and that this homodimer formation is indispensable for the integrity of complex I. These data suggest that the homodimer of Atg38 functions as a physical linkage between the Vps15-Vps34 and Atg14-Vps30 subcomplexes to facilitate complex I formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy*
  • Autophagy-Related Proteins
  • Class III Phosphatidylinositol 3-Kinases / genetics
  • Class III Phosphatidylinositol 3-Kinases / metabolism*
  • Gene Expression Regulation, Fungal
  • Genotype
  • Immunoprecipitation
  • Multiprotein Complexes
  • Mutation
  • Phenotype
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • Protein Multimerization
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Vacuolar Sorting Protein VPS15 / metabolism
  • Vesicular Transport Proteins / metabolism

Substances

  • Atg38 protein, S cerevisiae
  • Autophagy-Related Proteins
  • Multiprotein Complexes
  • Saccharomyces cerevisiae Proteins
  • VPS30 protein, S cerevisiae
  • Vesicular Transport Proteins
  • Class III Phosphatidylinositol 3-Kinases
  • VPS15 protein, S cerevisiae
  • Vacuolar Sorting Protein VPS15