Autophagy plays a WASHing game.

Beclin 1 is a crucial regulator of autophagy. It forms a complex with ATG14L, VPS34 or the class III phosphatidylinositol 3-kinase AMBRA1 to control autophagosome formation. A study in this issue of The EMBO Journal (Xia et al, 2013) reports that WASH, a protein known to regulate endosomal sorting, hampers autophagy by inhibiting the AMBRA1-dependent polyubiquitylation of Beclin 1. This modification is required to promote VPS34 activity and to initiate autophagy during starvation. Macroautophagy (hereafter called autophagy) is a lysosomal degradation pathway for cytoplasmic components. Autophagy is initiated by the formation of a doublemembrane bound vacuole, the autophagosome that sequesters the autophagic cargo and eventually fuses with the lysosomal compartment, leading to cargo degradation. Autophagy plays a major role in cytoplasm homeostasis by removing protein aggregates and controlling organelle quality, and it is stimulated to promote cell survival during stressful situations, such as nutrient starvation and microbial infection. Autophagosome formation is dependent on evolutionarily conserved Atg (Autophagy-related) proteins initially identified in yeast (Mizushima et al, 2011). They function in complexes or functional modules on a membrane known as the phagophore that matures into the autophagosome via several stages (initiation, elongation and sealing). Phosphatidylinositol 3-phosphate kinase complex I (PI3K complex I) plays a key role in the initiation step. In this complex, Beclin 1 (the mammalian homologue of yeast Atg6)