Effect of oxygen on activation state of complex I and lack of oxaloacetate inhibition of complex II in Langendorff perfused rat heart.
Two main entry points for electrons into the mitochondrial respiratory chain are NADH:ubiquinone oxidoreductase (complex I) and succinate:ubiquinone oxidoreductase (complex II). Metabolic regulation of these two respiratory complexes is not understood in detail. It has been suggested that the Krebs cycle metabolic intermediate oxaloacetate (OAA) inhibits complex II in vivo, whereas complex I undergoes a reversible active/de-active transition. In normoxic and anoxic hearts it has been shown that the proportion of complex I in the active and de-active states is different suggesting a possible mode of regulation of the enzyme by oxygen concentration. In the current studies rapid isolation of mitochondrial membranes in a state that preserves the activity of both complex I and complex II has been achieved using Langendorff perfused rat hearts. The findings indicate that the state of activation of complex I is controlled by the oxygen saturation in the perfusate. In addition, these studies show that complex II is fully active in the mitochondrion and not inhibited by OAA regardless of the oxygen concentration.
Maklashina
Elena
E
Molecular Biology Division, VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA. mclash@itsa.ucsf.edu
Kotlyar
Alexander B
AB
Karliner
Joel S
JS
Cecchini
Gary
G
D000818:Animals; D042967:Electron Transport Complex I / Q000378:metabolism*; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005650:Fumarates / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000201:enzymology; D008297:Male; D008314:Malonates / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000201:enzymology; D009097:Multienzyme Complexes / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D062907:Oxaloacetic Acid / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013385:Succinate Dehydrogenase / Q000378:metabolism
D005650:Fumarates; D008314:Malonates; D009097:Multienzyme Complexes; D062907:Oxaloacetic Acid; C032005:fumaric acid; C030290:malonic acid; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D011190:Potassium Cyanide; D010100:Oxygen