8.A.187. The Lipase Atg15 (Atg15) Family
Autophagy (see TC families 9.A.15, 9.B.26 and 9.B.134) is a cellular degradation process widely conserved among eukaryotes. During autophagy, cytoplasmic materials fated for degradation are compartmentalized in double membrane-bound organelles called autophagosomes. After fusing with the vacuole, their inner membrane-bound structures are released into the vacuolar lumen to become autophagic bodies and eventually degraded by vacuolar hydrolases. Atg15 is a lipase that is essential for disintegration of autophagic body membranes and has a transmembrane domain at the N-terminus and a lipase domain at the C-terminus. Hirata et al. 2021 found that the N-terminal domain alone can travel to the vacuole via the multivesicular body pathway, and that targeting of the C-terminal lipase domain to the vacuole is required for degradation of autophagic bodies. Moreover, the C-terminal domain could disintegrate autophagic bodies when it was transported to the vacuole via the Pho8 pathway instead of the multivesicular body pathway. H435 is one of the residues composing the putative catalytic triad, and W466 is an important residue for degradation of autophagic bodies. Thus, the C-terminal lipase domain recognizes autophagic bodies to degrade them (Hirata et al. 2021).