Lipid peroxidation and changes in the ubiquinone content and the respiratory chain enzymes of submitochondrial particles.
The relationship between, lipid peroxidation induced by ascorbate and adenosine ADP/Fe3+, and its effect on the respiratory chain activities of beef heart submitochondrial particles has been investigated. Lipid peroxidation, measured as thiobarbituric acid reactive substance formation, resulted in an inhibition of the NADH and succinate oxidase activities. Examination of several partial reactions of the respiratory chain revealed inactivation primarily of those involving endogenous ubiquinone, i.e., NADH- and succinate-ubiquinone1 and cytochrome c reductases. Ubiquinol-cytochrome c reductase, measured with reduced ubiquinone2 as electron donor, was unaffected. The amount of NADH- or succinate-reducible cytochrome b in the presence of cyanide was strongly decreased, but could be recovered by the addition of antimycin. There occurred a substantial decrease of the ubiquinone content in the course of lipid peroxidation, with a linear relationship between this decrease and the NADH and succinate oxidase activities. The results are consistent with the conclusion that the ubiquinone pool undergoes an oxidative modification during lipid peroxidation, to a form that can no longer function as a component of the respiratory chain. Lipid peroxidation also led to a partial inhibition of the succinate dehydrogenase and cytochrome c oxidase activities and a minor decrease of the cytochrome c and cytochrome a contents. Reduction of endogenous ubiquinone prevented lipid peroxidation as well as the concomitant modification of ubiquinone and inactivation of the respiratory chain. These observations suggest that the destruction of ubiquinone through lipid peroxidation is the primary cause of inactivation of the respiratory chain, and emphasize the antioxidant role of ubiquinol in preventing these effects. The possible implications of these findings for regulation of the cellular turnover of ubiquinone by the prevailing oxidative stress are discussed.
Forsmark-Andrée
P
P
Division for Medical Cell Biology, NOVUM, Karolinska Institute, Huddinge, Sweden.
Lee
C P
CP
Dallner
G
G
Ernster
L
L
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002417:Cattle; D003580:Cytochromes / Q000378:metabolism; D004579:Electron Transport; D005290:Ferric Compounds / Q000494:pharmacology; D007700:Kinetics; D015227:Lipid Peroxidation; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D013367:Submitochondrial Particles / Q000187:drug effects / Q000201:enzymology*; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
D003580:Cytochromes; D005290:Ferric Compounds; D013386:Succinates; D017392:Thiobarbituric Acid Reactive Substances; D009243:NAD; D014451:Ubiquinone; D000244:Adenosine Diphosphate; D019802:Succinic Acid; C003741:ubiquinol; D001205:Ascorbic Acid