Grevengoed 2015 J Lipid Res
|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.|
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
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