PtdIns 3-Kinase Orchestrates Autophagosome Formation in Yeast

Abstract

Eukaryotic cells can massively transport their own cytoplasmic contents into a lytic compartment, the vacuole/lysosome, for recycling through a conserved system called autophagy. The key process in autophagy is the sequestration of cytoplasmic contents within a double-membrane structure, the autophagosome. Autophagosome formation requires the elaborate cooperation of Atg ( a u t opha g y-related) proteins and lipid molecules. Phosphorylation of phosphatidylinositol (PtdIns) by a PtdIns 3-kinase, Vps34, is a key step in coordinating Atg proteins and lipid molecules. Vps34 forms two distinct protein complexes, only one of which is involved in generating autophagic membranes. Upon induction of autophagy, PtdIns(3) P , the enzymatic product of PtdIns 3-kinase, is massively transported into the lumen of the vacuole via autophagy. PtdIns(3) P is enriched on the inner membrane of the autophagosome. PtdIns(3) P recruits the Atg18−Atg2 complex and presumably other Atg proteins to autophagic membranes, thereby coordinating lipid molecules and Atg proteins.