Apg2 is a novel protein required for the cytoplasm to vacuole targeting, autophagy, and pexophagy pathways

To survive starvation conditions, eukaryotes have developed an evolutionari ly conserved process, termed autophagy, by which the vacuole/lysosome media tes the turnover and recycling of non-essential intracellular material for re-use in critical biosynthetic reactions. Morphological and biochemical st udies in Saccharomyces cerevisiae have elucidated the basic steps and mecha nisms of the autophagy pathway. Although it is a degradative process, autop hagy shows substantial overlap with the biosynthetic cytoplasm to vacuole t argeting (Cvt) pathway that delivers resident hydrolases to the vacuole. Re cent molecular genetics analyses of mutants defective in autophagy and the Cvt pathway, apg, aut, and cvt, have begun to identify the protein machiner y and provide a molecular resolution of the sequestration and import mechan ism that are characteristic of these pathways. In this study, we have ident ified a novel protein, termed Apg2, required for both the Cvt and autophagy pathways as well as the specific degradation of peroxisomes. Apg2 is requi red for the formation and/or completion of cytosolic, sequestering vesicles that are needed for vacuolar import through both the Cvt pathway and autop hagy. Biochemical studies revealed that Apg2 is a peripheral membrane prote in. Apg2 localizes to the previously identified perivacuolar compartment th at contains Apg9, the only characterized integral membrane protein that, is required for autophagosome/Cvt vesicle formation.