Formation of molecular species of mitochondrial cardiolipin. 1. A novel transacylation mechanism to shuttle fatty acids between sn-1 and sn-2 positions of multiple phospholipid species |
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Authors: | Ashim Malhotra Yang Xu Mindong Ren Michael Schlame |
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Institution: | 1. Department of Anesthesiology, New York University Langone Medical Center, New York, NY 10016, USA;2. Department Cell Biology, New York University Langone Medical Center, New York, NY 10016, USA |
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Abstract: | Mitochondrial cardiolipin undergoes extensive remodeling of its acyl groups to generate uniformly substituted species, such as tetralinoleoyl-cardiolipin, but the mechanism of this remodeling has not been elucidated, except for the fact that it requires tafazzin. Here we show that purified recombinant Drosophila tafazzin exchanges acyl groups between cardiolipin and phosphatidylcholine by a combination of forward and reverse transacylations. The acyl exchange is possible in the absence of phospholipase A2 because it requires only trace amounts of lysophospholipids. We show that purified tafazzin reacts with various phospholipid classes and with various acyl groups both in sn-1 and sn-2 position. Expression studies in Sf9 insect cells suggest that the effect of tafazzin on cardiolipin species is dependent on the cellular environment and not on enzymatic substrate specificity. Our data demonstrate that tafazzin catalyzes general acyl exchange between phospholipids, which raises the question whether pattern formation in cardiolipin is the result of the equilibrium distribution of acyl groups between multiple phospholipid species. |
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Keywords: | Acyl species are abbreviated X:Y where X specifies the number of carbon atoms and Y specifies the number of double bonds BEL bromoenol lactone CL cardiolipin DLCL dilyso-cardiolipin HPLC high-performance liquid chromatography LPC lyso-phosphatidylcholine MBP-TAZ fusion protein consisting of maltose-binding protein and full-length Drosophila tafazzin MLCL monolyso-cardiolipin PC phosphatidylcholine PE phosphatidylethanolamine PLA2 phospholipase A2 |
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