Defining the membrane precursor supporting the nucleation of the phagophore.

How does the phagophore form? Which membrane acts as a platform for its biogenesis? Over the years, extensive use of microscopy techniques have led to the controversial identification of multiple potential membranes as precursors for phagophore nucleation and/or for the supply of lipids to the expanding compartment. Nevertheless, none of these studies has established a direct functional link between membrane sources and autophagosome biogenesis. Addressing this point, in a recent study highlighted by a punctum in this issue, Ge and coworkers developed an in vitro approach to determine the identity of the membranes responsible for the lipidation of LC3, thus identifying the ER-Golgi intermediate compartment (ERGIC) as a potential key determinant of phagophore biogenesis.