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

Trisha J Grevengoed; Sarah A Martin; Lalage Katunga; Daniel E Cooper; Ethan J Anderson; Robert C Murphy; Rosalind A Coleman

doi:10.1194/jlr.M059717

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

Journal article

Open access

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

Trisha J Grevengoed, Sarah A Martin, Lalage Katunga, Daniel E Cooper, Ethan J Anderson, Robert C Murphy and Rosalind A Coleman

Journal of lipid research, Vol.56(8), pp.1572-1582

08/2015

DOI: 10.1194/jlr.M059717

PMCID: PMC4513998

PMID: 26136511

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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 (Acsl1T−/−) 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. Acsl1T−/− 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 Acsl1T−/− hearts, control and Acsl1T−/− 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.

heart fatty acid/metabolism

fatty acid/oxidation

phospholipids/metabolism

phospholipids/biosynthesis

cardiomyocyte dysfunction

Details

Title: Subtitle: Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function
Creators: Trisha J Grevengoed - Department of Nutrition, University of North Carolina at Chapel Hill, NC 27599
Sarah A Martin - Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
Lalage Katunga - Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC 27858
Daniel E Cooper - Department of Nutrition, University of North Carolina at Chapel Hill, NC 27599
Ethan J Anderson - Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC 27858
Robert C Murphy - Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
Rosalind A Coleman - Department of Nutrition, University of North Carolina at Chapel Hill, NC 27599
Resource Type: Journal article
Publication Details: Journal of lipid research, Vol.56(8), pp.1572-1582
DOI: 10.1194/jlr.M059717
PMID: 26136511
PMCID: PMC4513998
NLM abbreviation: J Lipid Res
ISSN: 0022-2275
eISSN: 1539-7262
Publisher: Elsevier Inc
Language: English
Date published: 08/2015
Academic Unit: Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology
Record Identifier: 9984065694002771

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