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

Françoise Hullin-Matsuda¹^,*^,^,, Kiyoshi Kawasaki^**, Isabelle Delton-Vandenbroucke^,, Yang Xu, Masahiro Nishijima, Michel Lagarde^,, Michael Schlame and Toshihide Kobayashi¹^,*^,^,

^* RIKEN, Wako-shi, Saitama 351-0198, Japan
Institut National de la Santé et de la Recherche Médicale U870, Institut National de la Recherche Agronomique U1235, Institut National des Sciences Appliquées de Lyon, University Lyon 1 and Hospices Civils de Lyon, 69621 Villeurbanne, France
Institut National de la Santé et de la Recherche Médicale-RIKEN Lipidomics Unit, Doshisha Women's College, Kodo, Kyotanabe-shi, Kyoto 610-0395, Japan
^** Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kodo, Kyotanabe-shi, Kyoto 610-0395, Japan
Department of Anesthesiology, New York University School of Medicine, New York, NY 10016
National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan

The online version of this article (available at http://www.jlr.org)contains supplementary data in the form of 3 Tables and 4 Figures.

Published, JLR Papers in Press, June 8, 2007.

^¹ To whom correspondence should be addressed. e-mail: hullin-matsuda{at}riken.jp (F.H-M.); kobayasi{at}riken.jp (T.K.)

Bis(monoacylglycero)phosphate (BMP) is a unique lipid enrichedin the late endosomes participating in the trafficking of lipidsand proteins through this organelle. The de novo biosynthesisof BMP has not been clearly demonstrated. We investigated whetherphosphatidylglycerol (PG) and cardiolipin (CL) could serve asprecursors of de novo BMP synthesis using two different cellularmodels: CHO cells deficient in phosphatidylglycerophosphate(PGP) synthase, the enzyme responsible for the first step ofPG synthesis; and human lymphoblasts from patients with Barthsyndrome (BTHS), characterized by mutations in tafazzin, anenzyme implicated in the deacylation-reacylation cycle of CL.The biosynthesis of both PG and BMP was reduced significantlyin the PGP synthase-deficient CHO mutants. Furthermore, overexpressionof PGP synthase in the deficient mutants induced an increaseof BMP biosynthesis. In contrast to CHO mutants, BMP biosynthesisand its fatty acid composition were not altered in BTHS lymphoblasts.Our results thus suggest that in mammalian cells, PG, but notCL, is a precursor of the de novo biosynthesis of BMP. Despitethe decrease of de novo synthesis, the cellular content of BMPremained unchanged in CHO mutants, suggesting that other pathway(s)than de novo biosynthesis are also used for BMP synthesis.

Supplementary key words endocytosis • phosphatidylglycerol • cardiolipin • Chinese hamster ovary cell mutant • Barth syndrome • mitochondria • lysobisphosphatidic acid

Abbreviations: BMP, bis(monoacylglycero)phosphate; BTHS, Barth syndrome; CL, cardiolipin; HPTLC, high-performance thin-layer chromatography; LE, late endosome; LPG, lysophosphatidylglycerol; MLCL, monolysocardiolipin; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PGP, phosphatidylglycerophosphate

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