C. elegans Screen Identifies Autophagy Genes Specific to Multicellular Organisms

SummaryThe 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 steps of the autophagy pathway. epg-2 encodes a coiled-coil 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. This study establishes C. elegans as a multicellular genetic model to delineate the autophagy pathway and provides mechanistic insights into the metazoan-specific autophagic process.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (303 K)Download as PowerPoint slideHighlights► Genetic screen in C. elegans identifies four metazoan-specific autophagy genes ► EPG-2, -3, -4, and -5 function at discrete steps of the autophagy pathway ► Mammalian homologs of EPG-3, -4, and -5 are essential for starvation-induced autophagy ► C. elegans is a useful model system to delineate the autophagy pathway