Four metazoan autophagy genes regulate cargo recognition, autophagosome formation and autolysosomal degradation

The mechanism responsible for induction and maturation of autophagosomes in multicellular organisms is poorly understood. We performed genetic screens in C. elegans and identified three essential autophagy genes, epg-3, -4 and -5, which have highly conserved homologs in mammals, but are absent in yeast. We also identified a nematode-specific gene, epg-2, that is required for degradation of components of the specialized protein aggregates, called PGL granules. epg-2, -3, -4 and -5 define discrete genetic steps of the autophagy pathway. We further demonstrated that mammalian homologs of EPG-3, -4 and -5 are essential for starvation-induced autophagy. Our study establishes C. elegans as a model to identify components of the basal autophagy pathway specific to higher eukaryotes and to further assemble these genes into genetic pathways.