The enzymatic function of tafazzin.
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.
Xu
Yang
Y
Departments of Anesthesiology and Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
Malhotra
Ashim
A
Ren
Mindong
M
Schlame
Michael
M
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000737:chemistry / Q000502:physiology*; D000215:Acylation; D000818:Animals; D016367:Baculoviridae / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism; D002460:Cell Line; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D007313:Insecta; D008928:Mitochondria / Q000378:metabolism; D008956:Models, Chemical; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D011485:Protein Binding; D013379:Substrate Specificity; D013997:Time Factors
D002308:Cardiolipins; D029721:Drosophila Proteins; D010713:Phosphatidylcholines; D010743:Phospholipids; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C514176:tafazzin protein, Drosophila