An understanding of de novo organelle construction comes one step closer thanks to He et al. (page 925), who find that Atg11 leads Atg9 to the preautophagosomal structure (PAS).

The PAS is intriguing because it is the site where fragments of membrane coalesce to form a new organelle: the autophagosome. In yeast, two flavors of this process exist. Bulk autophagy is induced by starvation and is essentially a cell nondiscriminately eating itself. The cytoplasm-to-vacuole targeting (Cvt) pathway, however, is constitutive and picks selected cargoes for delivery to the vacuole (the yeast equivalent of the lysosome).

Nobody knows what protein gets to the PAS first, but Atg9, as the first characterized transmembrane protein required for both pathways, is a good starting point. It cycles between the PAS and other sites, including mitochondria, probably as a way of collecting membrane fragments to build an autophagosome. It is not yet clear, however, what targets Atg9 to the PAS.

He et al. find that Atg11 uses one of its coiled coil regions to bind to Atg9, and this interaction and an intact actin cytoskeleton are required for Atg9's anterograde transport to the PAS. This transport mechanism is only required for the Cvt pathway; during bulk transport, another mechanism somehow ensures Atg9 cycling.

Both Atg9 and Atg11 have multiple binding partners, but further efforts will be needed to identify where in the autophagy pathway these interactions occur. An assay using semipermeabilized cells should help determine which complexes are most important for creating an autophagosome.