Autophagy is a cellular degradation system 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 essential for disintegration of autophagic body membranes and has a transmembrane domain at the N-terminus and a lipase domain at the C-terminus. However, the roles of both domains in vivo are not well understood. In this study, we 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, we found that 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. Finally, we identified H435 as one of the residues composing the putative catalytic triad, and W466 as an important residue for degradation of autophagic bodies. This study may provide a clue to understanding how the C-terminal lipase domain recognizes autophagic bodies to degrade them.

自噬是一种在真核生物中广泛保守的细胞降解系统。在自噬过程中，注定要降解的细胞质材料被分隔在称为自噬体的双膜结合细胞器中。与液泡融合后，它们的内膜结合结构被释放到液泡腔内成为自噬体，最终被液泡水解酶降解。Atg15 是自噬体膜分解所必需的脂肪酶，在 N 端具有跨膜结构域，在 C 端具有脂肪酶结构域。然而，这两个结构域在体内的作用不太了解。在这项研究中，我们发现单独的 N 端结构域可以通过多泡体途径到达液泡，并且自噬体降解需要将 C 端脂肪酶结构域靶向液泡。此外，我们发现当 C 端结构域通过 Pho8 途径而不是多泡体途径转运到液泡时，它可以分解自噬体。最后，我们确定 H435 是构成推定催化三联体的残基之一，W466 是降解自噬体的重要残基。这项研究可能为理解 C 端脂肪酶结构域如何识别自噬体以降解它们提供线索。