Atg8s in autophagy. (a) The conjugation of Atg8 proteins to phosphatidylethanolamine (PE) mediated by a series of steps involving Atg proteins. Following translation, Atg8 proteins are cleaved by the Atg4 protease at the carboxyl terminus to expose a glycine residue. This glycine is then activated by the E1-like enzyme Atg7 and transferred to the E2-like enzyme Atg3. Finally, the conjugation of Atg8 proteins to PE is mediated by the E3-like complex Atg5-Atg12-Atg16. The association of Atg8 proteins with the autophagic membrane is reversible and is mediated by Atg4. (b) The role of Atg8 proteins in the autophagic process. Atg8 proteins are recruited to the autophagic membrane together with autophagic cargo adaptors. On the autophagic membrane Atg8 proteins are conjugated to PE lipids, enabling them to mediate membrane fusion events leading to autophagosome biogenesis. Different Atg8 proteins recruit distinct adaptors and are therefore responsible for the delivery of specific cargo (protein aggregates, organelles such as mitochondria and pathogens) for lysosomal degradation.