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Journal of Lipid Research, Vol. 47, 1140-1145, June 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Short Communication

Cloning and characterization of a cDNA encoding human cardiolipin synthase (hCLS1)

Biao Lu^*, Fred Y. Xu, Yan J. Jiang^*, Patrick C. Choy, Grant M. Hatch, Carl Grunfeld and Kenneth R. Feingold^1,*,

^* Department of Dermatology, University of California, San Francisco, CA 94121
Departments of Pharmacology and Therapeutics, Biochemistry and Medical Genetics, and Internal Medicine and Center for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, Canada R3E 0T5
Department of Medicine, University of California, San Francisco, CA 94121

Published, JLR Papers in Press, March 18, 2006.

¹ To whom correspondence should be addressed. e-mail: kfngld{at}itsa.ucsf.edu

ABSTRACT

Cardiolipin (CL) is a phospholipid localized to the mitochondria, and its biosynthesis is essential for mitochondrial structure and function. We report here the identification and characterization of a cDNA encoding the first mammalian cardiolipin synthase (CLS1) in humans and mice. This cDNA exhibits sequence homology with members of a CLS gene family that share similar domain structure and chemical properties. Expression of the human CLS (hCLS1) cDNA in reticulocyte lysates or insect cells led to a marked increase in CLS activity. The enzyme is specific for CL synthesis, because no significant increase in phosphatidylglycerol phosphate synthase activity was observed. In addition, CL pool size was increased in hCLS1-overexpressing cells compared with controls. Furthermore, the hCLS1 gene was highly expressed in tissues such as heart, skeletal muscle, and liver, which have been shown to have high CLS activities. These results demonstrate that hCLS1 encodes an enzyme that synthesizes CL.

Supplementary key words mitochondria • phospholipid • diphosphatidylglycerol

Abbreviations: CDP-DG, cytidine-5'diphosphate-1,2-diacylglycerol; CL, cardiolipin; CLS, cardiolipin synthase; EST, expressed sequence tag; PG, phosphatidylglycerol; PGP, phosphatidylglycerol phosphate

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