The effect of reactive oxygen species generated from the mitochondrial electron transport chain on the cytochrome c oxidase activity and on the cardiolipin content in bovine heart submitochondrial particles.
The effect of reactive oxygen species (ROS), produced by the mitochondrial respiratory chain, on the activity of cytochrome c oxidase and on the cardiolipin content in bovine heart submitochondrial particles (SMP) was studied. ROS were produced by treatment of succinate-respiring SMP with antimycin A. This treatment resulted in a large production of superoxide anion, measured by epinephrine method, which was blocked by superoxide dismutase (SOD). Exposure of SMP to mitochondrial mediated ROS generation, led to a marked loss of cytochrome c oxidase activity and to a parallel loss of cardiolipin content. Both these effects were completely abolished by SOD+catalase. Added cardiolipin was able to almost completely restore the ROS-induced loss of cytochrome c oxidase activity. No restoration was obtained with peroxidized cardiolipin. These results demonstrate that mitochondrial mediated ROS generation affects the activity of cytochrome c oxidase via peroxidation of cardiolipin which is needed for the optimal functioning of this enzyme complex. These results may prove useful in probing molecular mechanism of ROS-induced peroxidative damage to mitochondria which have been proposed to contribute to aging, ischemia/reperfusion and chronic degenerative diseases.
Paradies
G
G
Department of Biochemistry and Molecular Biology and CNR Unit for the Study of Mitochondria and Bioenergetics, University of Bari, Italy. g.paradies@biologia.uniba.it
Petrosillo
G
G
Pistolese
M
M
Ruggiero
F M
FM
D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D002417:Cattle; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D017382:Reactive Oxygen Species; D013367:Submitochondrial Particles / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology
D002308:Cardiolipins; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV