Myocardial ischemia decreases oxidative phosphorylation through cytochrome oxidase in subsarcolemmal mitochondria.
The effect of myocardial ischemia on mitochondrial oxidative phosphorylation was investigated using isolated, buffer-perfused rabbit hearts. After 45 min of global ischemia, oxidative phosphorylation was decreased only in the subsarcolemmal population of mitochondria with all substrates tested. The oxidation of N,N,N',N' tetramethyl p-phenylenediamine-ascorbate, an electron donor to cytochrome oxidase via cytochrome c, was decreased in subsarcolemmal mitochondria [ischemia (n = 6): 76 +/- 3 vs. control (n = 5): 105 +/- 6 nanoatoms O.min-1.mg-1, P < 0.01] but not in interfibrillar mitochondria. Only minor morphological changes were observed by electron microscopy in the isolated mitochondria after ischemia. Neither cytochrome oxidase activity measured under conditions for maximal activity nor the apparent Michaelis constant and maximum velocity values of the two cytochrome c binding sites were different in subsarcolemmal mitochondria isolated from ischemic and control hearts. The cytochrome c content was decreased in subsarcolemmal mitochondria after ischemia (ischemia: 0.111 +/- 0.013 vs. control: 0.156 +/- 0.007 nmol/mg protein, P < 0.05). Thus ischemia decreased the rate of oxidative phosphorylation through cytochrome oxidase selectively in intact subsarcolemmal mitochondria. Ischemic damage to the terminal segment of the electron transport chain involves a decrease in the content of cytochrome c, whereas the expressible catalytic activity of cytochrome oxidase remains unchanged.
Lesnefsky
E J
EJ
Department of Medicine, Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
Tandler
B
B
Ye
J
J
Slabe
T J
TJ
Turkaly
J
J
Hoppel
C L
CL
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D066298:In Vitro Techniques; D007700:Kinetics; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010085:Oxidative Phosphorylation; D011817:Rabbits; D012508:Sarcolemma
D000244:Adenosine Diphosphate; D003576:Electron Transport Complex IV