The activation mechanism of Atg15, a vacuolar phospholipase required for the disintegration of organelle membranes

Autophagy. 2024 Mar 21. doi: 10.1080/15548627.2024.2333165. Online ahead of print.ABSTRACTThe disintegration of cytoplasm-to-vacuole targeting (Cvt) bodies and autophagic bodies in vacuoles is essential to the Cvt pathway and macroautophagy in yeast. Atg15 is a vacuolar lipase required for the degradation of both Cvt and autophagic bodies. However, the molecular mechanism of their degradation by Atg15 remains poorly understood. In a recent study, we showed that recombinant Chaetomium thermophilum Atg15 (CtAtg15) possesses phospholipase activity, and that this activity is significantly elevated by proteolytic cleavage at a site away from the active center. The proteolytic cleavage of CtAtg15 causes a conformational change around the active center, resulting in the active open state. Interestingly, activated CtAtg15 can degrade not only Cvt and autophagic bodies but also organelle membranes. On the basis of these results, we propose an activation mechanism by which Atg15, as an "organellase," functions only in vacuoles.PMID:38513722 | DOI:10.1080/15548627.2024.2333165

Source: Autophagy - March 21, 2024 Category: Cytology Authors: Yasunori Watanabe Kuninori Suzuki Source Type: research