The molecular understanding of autophagy has originated almost exclusively from yeast genetic studies. Little is known about essential autophagy components specific to higher eukaryotes. Here we perform genetic screens in C. elegans and identify four metazoan-specific autophagy genes, named epg-2, -3, -4, and -5. Genetic analysis reveals that epg-2, -3, -4, and -5 define discrete genetic stepsof the autophagy pathway. epg-2 encodes a coiledcoil protein that functions in specific autophagic cargo recognition. Mammalian homologs of EPG-3/VMP1, EPG-4/EI24, and EPG-5/mEPG5 are essential for starvation-induced autophagy. VMP1 regulates autophagosome formation by controlling the duration of omegasomes. EI24 and mEPG5 are required for formation of degradative autolysosomes. Thisstudy establishes C. elegans as a multicellular genetic model to delineate the autophagy pathway and provides mechanistic insights into the metazoan-specific autophagic process.

Tian Y, Li ZP, Hu WQ, Ren HY, Tian E, Zhao Y, Lu Q, Huang XX, Yang PG, Li X, Wang XC, Attila LK, Yu L, Zhang H. C. elegans Screen Identifies Autophagy Genes Specific to Multicellular Organisms. Cell 2010,141:1042-1055.