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

ABSTRACT

The 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.

KEYWORDS:

• Atg15
• autophagic body
• organelle membrane
• phospholipase
• vacuolar proteases
• yeast

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant from the Naito Foundation (to K.S.), by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (22K06096 and 22H02569 to Y.W.; 20H05313, 21K19205, and 22H02569 to K.S.), and by CREST, the Japan Science and Technology Agency, Japan (JP201032912 to K.S.).