Atg4

Atg4 is the sole cysteine protease among dozens of Atg proteins and functions as an essential factor in the Atg8 conjugation system. While only one Atg4 is present in yeast, there are four Atg4 homologues (Atg4A, Atg4B, Atg4C, and Atg4D) in human and in mouse with different substrate specificities and catalytic efficiencies. Atg4 cleaves Atg8 at the peptide bond on the glycine residue at the C-terminus, thus allowing the conjugation of Atg8 to phosphatidylethanolamine (PE) with the participation of other autophagy molecules. Atg4 can also serve as a deconjugating enzyme, which cleaves the amide bond of the conjugated Atg8 and releases it from the autophagosomal membrane. The latter step is important for reusing Atg8 upon autophagy completion. Moreover, this deconjugation process may also occur on isolation membrane, which would positively or negatively affect membrane formation.