J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M700154-JLR200 on June 8, 2007

Papers In Press, published online ahead of print September 1, 2007
J. Lipid Res., doi:10.1194/jlr.M700154-JLR200
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Journal of Lipid Research, Vol. 48, 1997-2008, September 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

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

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

* RIKEN, Wako-shi, Saitama 351-0198, Japan
{dagger} 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
{dagger}{dagger} Department of Anesthesiology, New York University School of Medicine, New York, NY 10016
§§ National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan

boxs 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 enriched in 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 (PG) and cardiolipin (CL) could serve as precursors of de novo BMP synthesis using two different cellular models: CHO cells deficient in phosphatidylglycerophosphate (PGP) synthase, the enzyme responsible for the first step of PG synthesis; and human lymphoblasts from patients with Barth syndrome (BTHS), characterized by mutations in tafazzin, an enzyme implicated in the deacylation-reacylation cycle of CL. The biosynthesis of both PG and BMP was reduced significantly in the PGP synthase-deficient CHO mutants. Furthermore, overexpression of 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 BTHS lymphoblasts. Our results thus suggest that in mammalian cells, PG, but not CL, is a precursor of the de novo biosynthesis of BMP. Despite the decrease of de novo synthesis, the cellular content of BMP remained 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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