During autophagy induction in Saccharomyces cerevisiae, over twenty autophagy-related (Atg) proteins localize to the site of autophagosome formation to generate the pre-autophagosomal structure (PAS), where phase-separated condensates of the Atg1 kinase complex serve as a scaffold for recruiting other Atg proteins. The lipid transfer protein Atg2 forms a complex with the phosphatidylinositol 3-phosphate (PI3P)-binding protein Atg18 and mediates lipid influx from the endoplasmic reticulum to the PAS for membrane expansion. In this study, we discover that the Atg2-Atg18 complex interacts with the Atg1 complex. This interaction involves the C-terminal regions of Atg2 and the Atg1 complex subunit Atg29, and is enhanced by Atg1-dependent phosphorylation of Atg29. This interaction, together with Atg18 binding to PI3P, promotes PAS localization of the Atg2-Atg18 complex. These findings provide new insight into PAS organization and highlight the Atg1 complex as a central hub coordinating Atg protein assembly during autophagosome formation.
Yasuda et al. (Wed,) studied this question.