Mitochondrial complexes I, II, III, IV, and V in myocardial ischemia and autolysis

Abstract

Ischemic myocardium was produced by occluding the left circumflex coronary artery in anesthetized dogs. Autolyzed myocardium was produced by incubating transmural samples of canine left ventricle at 37 degrees C. Tissue pH was recorded continuously in each model using a microcombination pH electrode impaled into the midmyocardium. The activities of the five mitochondrial inner membrane enzyme complexes of electron transport and coupled oxidative phosphorylation were assayed as a function of time of ischemia or autolysis. While the activities of complex II (succinate-CoQ reductase) and IV (cytochrome c oxidase) were completely stable, that of complex I (NADH-CoQ reductase) decreased markedly, but largely only after 20 min of ischemia or autolysis. At 20 min and beyond, the decrease in the activity of complex I paralleled closely the decrease in whole mitochondrial oxygen uptake with NAD-linked substrates in both models. The activity of complex III (CoQH2-c reductase) decreased at a more gradual rate during ischemia or autolysis, and its rate of decrease paralleled that of succinate-supported oxygen uptake. The activity of complex V (oligomycin-sensitive ATPase) decreased most rapidly (by 40% in only 5 min of autolysis) but nearly leveled off beyond 20 min in the two models. A strikingly similar pattern of differential enzyme lability was observed in isolated control mitochondria incubated at lowered pH values. The results demonstrate 1) differential enzyme lability within the mitochondrial inner membrane, 2) a connection between severity of acidosis and the degree of enzyme activity loss, and 3) the usefulness of simple tissue autolysis as an analogue of in situ myocardial ischemia.

Renoprotective effect of berberine via intonation on apoptosis and mitochondrial-dependent pathway in renal ischemia reperfusion-induced mutilation

“…Many pollsters have reported an influential role of Bcl-2 genes in commencement of caspase via affect on cytochrome C release from mitochondria. 77 Tremendous variations within mitochondria occur as a corollary of extended ischemia, which remarkably diminished the activity of cytochrome oxidase (complex IV) 78 which are in accordance with our investigation.…”

Temperature Threshold and Preservation of Signaling for Mitochondrial Membrane Proteins during Ischemia in Rabbit Heart

“…The adenine nucleotide translocator and the ␤F1-ATPase together account for greater than 30% of mitochondrial protein (12). Logically, one might assume that restoration of normal mitochondrial function following ischemic injury would require resynthesis and/or reconfiguration of these major mitochondrial membrane proteins (1,4,10,11,23,32,37). As expression of the adenine nucleotide translocator protein in particular closely coordinates with steady-state mRNA levels for the corresponding gene (31), one would expect that preserved gene expression would be necessary for eventual protein resynthesis.…”

Mitochondria: A mirror into cellular dysfunction in heart disease

“…As a result, the OxPhos pathway of the mitochondria has been the subject of numerous investigations. Complex 1 of the OxPhos pathway has been shown to be affected by I/R [20,[90][91][92][93], whereby the activity of the complex is significantly reduced, with concurrent changes in the abundance of several complex 1 subunits, as identified by proteomic techniques including 2-DE [76,94]. To investigate the discrete compositional alterations with I/R, isolated mitochondria treated with elevated levels of ROS and/or NO resulted in the inactivation of complex 1 [95][96][97][98][99][100][101], with in vitro preparations showing a similar inactivation of complex 1 by increased concentration of both ROS and Ca 21 [102].…”

“…Transient ischemia that injures in the absence of cell death results in cyto-protective conditioning (preconditioning (PC); post-conditioning (PostC)), producing adaptive modifications that are suggested to be mediated by mitochondrial channels [17,18]. During the early, reversible phases of ischemic injury, also termed myocardial stunning, the mitochondria are subjected to numerous functional changes [19], which progress with duration of ischemia [19,20]. Longer periods of ischemia have been shown to influence mitochondrial function via Ca 21 loading [21] and reduced levels of intrinsic ROS scavengers, including manganese superoxide dismutase [22].…”