Autophagy is a catabolic process for the autophagosomic-lysosomal degradation of bulk cytoplasmic contents . It is generally activated by conditions of nutrient deprivation but is also associated with a number of physiological processes including development, differentiation, neurodegeneration, infection, and cancer . The molecular machinery of autophagy was largely discovered in yeast and is directed by a number of autophagy-related (Atg) genes.
Vacuolar trafficking and autophagy are controlled by the class III type phosphoinositide 3-kinase (PI3K) Vps34, which generates phosphoinositide-3-phosphate (PtdIns3P) . Atg18 and Atg21 are two related WD-repeat proteins that bind PtdIns3P via a conserved Phe-Arg-Arg-Gly motif . It has been shown that Atg18 binds to Atg2 and that this complex is directed to vacuolar membranes by its interaction with PtdIns3P (8). Human orthologs of Atg18 and Atg21 were identified as members of the WD-repeat protein Interacting with Phosphoinositides (WIPI) family . WIPI1 (also called WIPI49) and WIPI2 have been shown to translocate from several vacuolar compartments to LC3-positive autophagosomes during autophagy; this translocation may be used as an autophagy marker .