The differential effects of superoxide anion, hydrogen peroxide and hydroxyl radical on cardiac mitochondrial oxidative phosphorylation.
The involvement of reactive oxygen species (ROS) in cardiac ischemia-reperfusion injuries is well-established, but the deleterious effects of hydrogen peroxide (H(2)O(2)), hydroxyl radical (HO*) or superoxide anion (O(2)*(-) ) on mitochondrial function are poorly understood. Here, we report that incubation of rat heart mitochondria with each of these three species resulted in a decline of the ADP-stimulated respiratory rate but not substrate-dependent respiration. These three species reduced oxygen consumption induced by an uncoupler without alteration of the respiratory chain complexes, but did not modify mitochondrial membrane permeability. HO* slightly decreased F1F0-ATPase activity and HO* and O(2)*(-) partially inhibited the activity of adenine nucleotide translocase; H(2)O(2) failed to alter these targets. They inhibited NADH production by acting specifically on aconitase for O(2)*(-) and alpha-ketoglutarate dehydrogenase for H(2)O(2) and HO*. Our results show that O(2)*(-), H(2)O(2) and HO* act on different mitochondrial targets to alter ATP synthesis, mostly through inhibition of NADH production.
Zini
Roland
R
INSERM, U841, Créteil, F-94010, France.
Berdeaux
Alain
A
Morin
Didier
D
D000818:Animals; D000838:Anions / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D017665:Hydroxyl Radical; D007655:Ketoglutarate Dehydrogenase Complex / Q000737:chemistry; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000737:chemistry; D010085:Oxidative Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000737:chemistry*
D000838:Anions; D009243:NAD; D013481:Superoxides; D017665:Hydroxyl Radical; D000226:Mitochondrial ADP, ATP Translocases; D006861:Hydrogen Peroxide; D007655:Ketoglutarate Dehydrogenase Complex