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J Lipid Res. 2015 Aug;56(8):1572-82. doi: 10.1194/jlr.M059717. Epub 2015 Jul 1.

Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function.

Author information

1
Department of Nutrition, University of North Carolina at Chapel Hill, NC 27599.
2
Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045.
3
Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC 27858.

Abstract

Long-chain acyl-CoA synthetase 1 (ACSL1) contributes more than 90% of total cardiac ACSL activity, but its role in phospholipid synthesis has not been determined. Mice with an inducible knockout of ACSL1 (Acsl1(T-/-)) have impaired cardiac fatty acid oxidation and rely on glucose for ATP production. Because ACSL1 exhibited a strong substrate preference for linoleate, we investigated the composition of heart phospholipids. Acsl1(T-/-) hearts contained 83% less tetralinoleoyl-cardiolipin (CL), the major form present in control hearts. A stable knockdown of ACSL1 in H9c2 rat cardiomyocytes resulted in low incorporation of linoleate into CL and in diminished incorporation of palmitate and oleate into other phospholipids. Overexpression of ACSL1 in H9c2 and HEK-293 cells increased incorporation of linoleate into CL and other phospholipids. To determine whether increasing the content of linoleate in CL would improve mitochondrial respiratory function in Acsl1(T-/-) hearts, control and Acsl1(T-/-) mice were fed a high-linoleate diet; this diet normalized the amount of tetralinoleoyl-CL but did not improve respiratory function. Thus, ACSL1 is required for the normal composition of several phospholipid species in heart. Although ACSL1 determines the acyl-chain composition of heart CL, a high tetralinoleoyl-CL content may not be required for normal function.

KEYWORDS:

cardiomyocyte dysfunction; fatty acid/oxidation; heart fatty acid/metabolism; phospholipids/biosynthesis; phospholipids/metabolism

PMID:
26136511
PMCID:
PMC4513998
DOI:
10.1194/jlr.M059717
[Indexed for MEDLINE]
Free PMC Article

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