De novo biosynthesis of the late endosome lipid, bis(monoacylglycero)phosphate

Francoise Hullin-Matsuda, Kiyoshi Kawasaki, Isabelle Delton-Vandenbroucke, Yang Xu, Masahiro Nishijima, Michel Lagarde, Michael Schlame, and Toshihide Kobayashi

Lipid Biology Laboratory, RIKEN, Wako, Saitama 351-0198

Corresponding Author: kobayasi{at}riken.jp

Bis(monoacylglycero)phosphate (BMP) is a unique lipid enriched in the the late endosomes participating in the trafficking of lipids and proteins through this organelle. The de novo biosynthesis of BMP has not been clearly demonstrated. We investigated whether phosphatidylglycerol and cardiolipin could serve as precursors of de novo BMP synthesis using two different cellular models: Chinese hamster ovary (CHO) cells deficient in phosphatidylglycerophosphate (PGP) synthase, the enzyme responsible for the first step of phosphatidylglycerol synthesis and human lymphoblasts from patients with Barth syndrome characterized by mutations in tafazzin, an enzyme implicated in the deacylation-reacylation cycle of cardiolipin. The biosynthesis of both phosphatidylglycerol and BMP was significantly reduced in the PGP synthase-deficient CHO mutants. Furthermore, overexpression of the PGP synthase in the deficient mutants induced an increase of BMP biosynthesis. In contrast to CHO mutants, BMP biosynthesis and its fatty acid composition were not altered in Barth syndrome lymphoblasts. Our results thus suggest that in mammalian cells, phosphatidylglycerol, but not cardiolipin, is a precursor of the de novo biosynthesis of BMP. Despite the decrease of de novo synthesis, cellular content of BMP remained unchanged in CHO mutants, suggesting that other pathway(s) than de novo biosynthesis are also used for BMP synthesis.

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