Atg21 regulates pexophagy via its PI(3)P-binding activity in Pichia pastoris.

Pexophagy is a selective degradation pathway of peroxisomes. In the present study, we revealed that PpAtg21 was required for pexophagy in the methylotrophic yeast Pichia pastoris. PpAtg21 was essential for efficient lipidation of Atg8 and for de novo synthesis of pexophagic membranes. In contrast to PpAtg18, PpAtg21 was not necessary for vacuolar fission nor invagination during micropexophagy. PpAtg21 specifically bound to PI(3)P, but not to PI(3,5)P2 in vitro, and the localization analyses matched with this phosphoinositide-binding specificity. The mutant which lost the lipid-binding activity showed defect in pexophagy, suggesting that PI(3)P-binding activity of PpAtg21 was required for pexophagy.