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J. Biol. Chem., Vol. 281, Issue 51, 39217-39224, December 22, 2006
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The Enzymatic Function of Tafazzin*
1
From the
Departments of Anesthesiology and Cell Biology, New York University School of Medicine, New York, New York 10016
Tafazzin is a putative enzyme that is involved in cardiolipin metabolism, it may carry mutations responsible for Barth syndrome. To identify the biochemical reaction catalyzed by tafazzin, we expressed the full-length isoform of Drosophila melanogaster tafazzin in a baculovirus-Sf9 insect cell system. Tafazzin expression induced a new enzymatic function in Sf9 cell mitochondria, namely 1-palmitoyl-2-[14C]linoleoyl-phosphatidylcholine:monolysocardiolipin linoleoyltransferase. We also found evidence for the reverse reaction, because tafazzin expression caused transfer of acyl groups from phospholipids to 1-[14C]palmitoyl-2-lyso-phosphatidylcholine. An affinity-purified tafazzin construct, tagged with the maltose-binding protein, catalyzed both forward and reverse transacylations between cardiolipin and phosphatidylcholine, but was unable to utilize CoA or acyl-CoA as substrates. Whereas tafazzin supported transacylations between various phospholipid-lysophospholipid pairs, it showed the highest rate for the phosphatidylcholine-cardiolipin transacylation. Transacylation activities were about 10-fold higher for linoleoyl groups than for oleoyl groups, and they were negligible for arachidonoyl groups. The data show that Drosophila tafazzin is a CoA-independent, acyl-specific phospholipid transacylase with substrate preference for cardiolipin and phosphatidylcholine.
Received for publication, June 26, 2006 , and in revised form, October 24, 2006.
* This work was supported in part by grants from the National Institutes of Health (1 R01 HL078788-01 A1, to M. S.), the American Heart Association (0350126N, to M. S.), and the Barth Syndrome Foundation (to Y. X. and M. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: Dept. of Anesthesiology, NYU School of Medicine, 550 First Ave., NY, NY 10016. Tel.: 212-2630648; Fax: 212-2636139; E-mail: michael.schlame{at}med.nyu.edu.
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