Grevengoed 2015 J Lipid Res

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Grevengoed TJ, Martin SA, Katunga L, Cooper DE, Anderson EJ, Murphy RC, Coleman RA (2015) Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function. J Lipid Res 56:1572-82.

» PMID: 26136511 Open Access

Grevengoed TJ, Martin SA, Katunga L, Cooper DE, Anderson EJ, Murphy RC, Coleman RA (2015) J Lipid Res

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.

Keywords: Cardiomyocyte dysfunction, Fatty acid/Oxidation, Heart fatty acid/Metabolism, Phospholipids/Biosynthesis, Phospholipids/Metabolism, Buffer z, Amplex Red, Calcium Green 5-N

O2k-Network Lab: US NC Greenville Anderson EJ, US NC Greenville Neufer PD


Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Heart, Other cell lines, HEK  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS  Pathway: F, N, NS, ROX  HRR: Oxygraph-2k