Assembly and function of membrane-scaffolds in autophagy
Final Report Abstract
Autophagosomes deliver superfluous or damaged cytosolic components to lysosomal compartments for degradation. Autophagic membranes engulf such material with high selectivity and specificity. Starvation, however, induces the formation of large autophagosomes that capture cytoplasm non-selectively. The formation of both types of autophagosomes depends on the conjugation of the small ubiquitin (Ub)-like protein Atg8 to the phagophore. The conjugation reaction is driven by a Ub-like conjugation machinery, which is recruited to the phagophore by upstream factors including Atg21. Here, we demonstrate that the PROPPINs Atg18 and Atg21 cooperate to form selective and nonselective autophagosomes. Atg21 facilitates bulk Atg8-lipidation at the phagophore, allowing the membrane to expand in the absence of templating cargo. Atg18, on the other hand, is sufficient to generate a lipidated Atg8-pool which tethers cargo to the growing phagophore. Our results thus imply that distinct functions of Atg21 and Atg18 at autophagic membranes are crucial to regulate the formation of either selective or non-selective autophagosomes.
