Impaired function of mitochondrial electron transfer complex I in canine myocardial ischemia: loss of flavin...

Regional myocardial ischemia was produced in anesthetized dogs by occluding the left branch of the circumflex coronary artery. After 30 or 60 min of occlusion, mitochondria were isolated from both non-ischemic (control) and ischemic transmural samples of the left ventricle and septum. Mitochondria from 60 min ischemic myocardium exhibited a drop in NAD-linked state 3 respiratory rates to 56 +/- 3% of controls and a parallel loss of NADH-CoQ reductase activity to 54 +/- 4% of controls. Analyses of two non-protein components of electron transfer complex I in mitochondria isolated from 60 min ischemic myocardium revealed a decrease in acid-extractable flavin mononucleotide (FMN) to 58 +/- 5% of controls and a small decrease in ubiquinone to 89 +/- 2% of controls. The observed dissociation and apparent washout of non-covalently-bound FMN from the ischemically damaged mitochondria thus accounted nearly quantitatively for the proportionate decrease seen in NADH-CoQ reductase activity and in state 3 respiration with NAD-linked substrates.