The lipid scramblase ATG9 is transported along axonal microtubules to presynaptic sites by the kinesin motor protein KIF1A/Unc104. ATG9-containing vesicles undergo activity-dependent cycling near the active zone (AZ) of transmitter release, mirroring the exocytosis and endocytosis steps of synaptic vesicles (SVs). Endocytosed ATG9 vesicles can acquire membranes from the ER/Golgi intermediate compartment (ERGIC) and possibly thetrans-Golgi network (TGN) as well as the plasma membrane. Consequently, the membranes that seed the phagophore, initially formed at the phagophore initiation site at the ER, are derived from these diverse sources (indicated by different colors in magnified insert). Phagophore membrane expansion depends on a lipid transport conduit from the ER to autophagosomes formed by the rod-shaped bridge-like lipid transport protein ATG2 and the lipid scramblase ATG9 (magnified inset on the right). As the phagophore elongates, the opposing membranes fuse, forming a mature autophagosome.
