PLA2G15 is a BMP hydrolase and its targeting ameliorates lysosomal disease.

ABSTRACT: Lysosomes catabolize lipids and other biological molecules, maintaining cellular and organismal homeostasis. Bis(monoacylglycero)phosphate (BMP), a major lipid constituent of intralysosomal vesicles, stimulates lipid-degrading enzymes and is altered in various human conditions, including neurodegenerative diseases^1,2. Although lysosomal BMP synthase was recently discovered³, the enzymes mediating BMP turnover remain elusive. Here we show that lysosomal phospholipase PLA2G15 is a physiological BMP hydrolase. We further demonstrate that the resistance of BMP to lysosomal hydrolysis arises from its unique sn2, sn2' esterification position and stereochemistry, as neither feature alone confers resistance. Purified PLA2G15 catabolizes most BMP species derived from cell and

SUBMITTER: Nyame K 

PROVIDER: S-EPMC12158761 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature