Lipid Transport from Endoplasmic Reticulum to Autophagic Membranes

Autophagy is an intracellular degradation system involving de novo generation of autophagosomes, which function as a transporting vesicle of cytoplasmic components to lysosomes for degradation. Isolation membranes (IMs) or phagophores, the precursor membranes of autophagosomes, require millions of phospholipids to expand and transform into autophagosomes, with the endoplasmic reticulum (ER) being the primary lipid source. Recent advances in structural and biochemical studies of autophagy-related proteins have revealed their lipid transport activities: Atg2 at the interface between IM and ER possesses intermembrane lipid transfer activities, while Atg9 at IM and VMP1 and TMEM41B at ER possess lipid scrambling activities. In this review, we summarize recent advances in the establishment of the lipid transport activities of these proteins and their collaboration mechanisms for lipid transport between the ER and IM, and further discuss how unidirectional lipid transport from the ER to IM occurs during autophagosome formation.