Volska 2018 MiP2018
The accumulation of long-chain acylcarnitines is observed in the ischemic myocardium and there is evidence that long-chain acylcarnitines determine the ischemia/reperfusion-induced damage in heart mitochondria. The aim of this study was to identify the mechanisms of long-chain acylcarnitine accumulation in the heart mitochondria during ischemia.
To study long-chain acylcarnitine accumulation in mitochondrial fractions, labelled [3H]-palmitoyl-carnitine content was measured in the inner and outer mitochondrial membranes, intermembrane space and mitochondrial matrix. To clarify the possible mechanisms of long-chain acylcarnitine accumulation during ischemia, mitochondrial respiration with palmitoyl-CoA, the activity of carnitine palmitoyltransferase (CPT) 1, CPT2-dependent β-oxidation, concentrations of acyl-CoA and CoA were measured in mitochondria isolated from the non-risk area and the area at risk of ischemic hearts.
Results indicated that the main locations of palmitoyl-carnitine accumulation are the inner mitochondrial membrane and the intermembrane space. Mitochondria isolated from area at risk had a 25% lower mitochondrial respiration rate with palmitoyl-CoA compared with those in non-risk area. The CPT1 activity in the area at risk was increased by 40%, whereas CPT2-dependent β-oxidation was decreased by 42% compared with the non-risk area. The ratio of acyl-CoA/CoA in the area at risk was almost 3-fold higher compared with that in the non-risk area, indicating that mitochondrial CoA pool is depleted.
In conclusion, long-chain acylcarnitine accumulation in the mitochondrial intermembrane space is a result of increased CPT1 activity and decreased CPT2-dependent fatty acid metabolism in mitochondria of ischemic myocardium.
Labels: MiParea: Respiration
Tissue;cell: Heart Preparation: Isolated mitochondria
Regulation: Fatty acid
Volska K(1,2), Liepinsh E(1), Makarova E(1), Makrecka-Kuka M(1), Kuka J(1), Dambrova M(1,2)
- Latvian Inst Organic Synthesis
- Riga Stradins Univ, Fac Pharmacy; Riga, Latvia