Remodeling of Cardiolipin by Phospholipid Transacylation

Mitochondrial cardiolipin (CL) contains unique fatty acid patterns, but it is not known how the characteristic molecular species of CL are formed. We found a novel reaction that transfers acyl groups from phosphatidylcholine or phosphatidylethanolamine to CL in mitochondria of rat liver and human ly...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-12, Vol.278 (51), p.51380-51385
Main Authors: Xu, Yang, Kelley, Richard I., Blanck, Thomas J.J., Schlame, Michael
Format: Article
Language:English
Subjects:
Acylation
Acyltransferases - metabolism
Animals
Carbon Radioisotopes
Cardiolipins - metabolism
Case-Control Studies
Humans
Lipid Metabolism, Inborn Errors - metabolism
Lymphocytes - metabolism
Mitochondria, Liver - metabolism
Phosphatidylcholines - metabolism
Phosphatidylethanolamines - metabolism
Proteins - metabolism
Rats
Transcription Factors
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Summary:Mitochondrial cardiolipin (CL) contains unique fatty acid patterns, but it is not known how the characteristic molecular species of CL are formed. We found a novel reaction that transfers acyl groups from phosphatidylcholine or phosphatidylethanolamine to CL in mitochondria of rat liver and human lymphoblasts. Acyl transfer was stimulated by ADP, ATP, and ATPγS, but not by other nucleotides. Coenzyme A stimulated the reaction only in the absence of adenine nucleotides. Free fatty acids were not incorporated into CL under the same incubation condition. The transacylation required addition of exogenous CL or monolyso-CL, whereas dilyso-CL was not a substrate. Transacylase activity was decreased in lymphoblasts from patients with Barth syndrome (tafazzin deletion), and this was accompanied by drastic changes in the molecular composition of CL. In rat liver, where linoleic acid was the most abundant residue of CL, only linoleoyl groups were transferred into CL, but not oleoyl or arachidonoyl groups. We demonstrated complete remodeling of tetraoleoyl-CL to tetralinoleoyl-CL in rat liver mitochondria and identified the intermediates linoleoyl-trioleoyl-CL, dilinoleoyl-dioleoyl-CL, and trilinoleoyl-oleoyl-CL by high-performance liquid chromatography. The data suggest that CL is remodeled by acyl specific phospholipid transacylation and that tafazzin is an acyltransferase involved in this mechanism.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M307382200