Makrecka-Kuka 2016 Abstract MitoFit Science Camp 2016
|Long-chain acylCoAs vs acylcarnitines in mitochondrial bioenergetics: from in vitro to in vivo.|
Fatty acid metabolism plays an essential role in muscles bioenergetics. The accumulation of long-chain fatty acids and their activated intermediates, CoA and carnitine esters, is observed in the ischemic myocardium after acute ischemia-reperfusion. The aim of the study was to compare long-chain acyl-CoAs and acylcarnitine effects on mitochondrial bioenergetics and identify harmful fatty acid intermediates.
The acute effects of palmitoyl-CoA and palmitoylcarnitine were studied in isolated rat cardiac mitochondria. To study the effects in vivo, pharmacological regulation of the availability of activated fatty acids by meldonium and methyl-GBB were used.
Palmitoylcarnitine, but not palmitoyl-CoA, was able to significantly reduce the pyruvate oxidation rate in mitochondria. Both palmitoyl-CoA and palmitoylcarnitine decreased OXPHOS-dependent mitochondrial respiration in dose-dependent manner. Despite that palmitoyl-CoA is approximately 2.5 times more toxic than palmitoylcarnitine, cardiac mitochondria are better protected against acyl-CoAs than against acylcarnitines due to protection by acyl-CoA-binding protein. Moreover, in ischemic mitochondria the content of long-chain acyl-CoAs was up to 50-fold lower than the measured acylcarnitine content. The pharmacological reduction of long-chain acylcarnitine content in mitochondria decreases ischemia-reperfusion induced mitochondrial dysfunction and significantly decreases infarct size.
Overall, present results demonstrate that long-chain acylcarnitines, but not long-chain acyl-CoAs, orchestrate mitochondrial energy metabolism pattern and determine ischemia-reperfusion induced damage in cardiac mitochondria.
• O2k-Network Lab: LV Riga Makrecka-Kuka M
Labels: MiParea: mt-Biogenesis;mt-density
Stress:Ischemia-reperfusion Organism: Rat Tissue;cell: Heart Preparation: Isolated mitochondria
Coupling state: OXPHOS Pathway: F
Event: A1 MitoFit Science Camp 2016
1-Latvian Inst Organic Synthesis, Lab Pharmaceutical Pharmacol; 2-Riga Stradins Univ, Fac Pharmacy, Riga, Latvia. - [email protected]