Cw. Wang et al., Apg2 is a novel protein required for the cytoplasm to vacuole targeting, autophagy, and pexophagy pathways, J BIOL CHEM, 276(32), 2001, pp. 30442-30451
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.