Benzoyl peroxide interaction with mitochondria: inhibition of respiration and induction of rapid, large-amplitude swelling.
When micromolar concentrations of benzoyl peroxide (BPO) are added to rat liver mitochondria, inhibition of mitochondrial NADH-oxidase and succinoxidase is observed. The addition of 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation, results in only partial release of this inhibition, suggesting that BPO inhibits both electron and energy transfer in mitochondria. Release of inhibition is also observed when an electron donor, N,N,N',N'-tetramethyl-p-phenylenediamine, is added, suggesting that inhibition occurs on the substrate side of cytochrome c. When BPO is added to respiring submitochondrial particles, only reduced cytochrome b is observed to accumulate in the difference spectrum (reduced minus oxidized) in a manner analogous to that observed in the presence of antimycin A. These results indicate that BPO interacts at coupling site II between cytochromes b and c1. When respiring SMP are treated with BPO in the presence of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide, electron spin resonance signals attributable to the hydroxyl and superoxide adducts are observed. Catalase and superoxide dismutase inhibit the formation of these adducts, suggesting the involvement of both hydrogen peroxide and superoxide radicals in this process. BPO also induces rapid, large-amplitude swelling of mitochondria; the swelling is dependent on the presence of monovalent cations but is independent of the presence of calcium, oxygen, and respiratory substrate. BPO-induced swelling appears to be disassociated from radical production and lipid peroxidation.
Kennedy
C H
CH
Biodynamics Institute, Louisiana State University, Baton Rouge 70803.
Winston
G W
GW
Church
D F
DF
Pryor
W A
WA
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001585:Benzoyl Peroxide / Q000494:pharmacology*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002414:Cations, Monovalent; D003580:Cytochromes / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D004735:Energy Transfer / Q000187:drug effects; D005609:Free Radicals; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008933:Mitochondrial Swelling / Q000187:drug effects; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D009840:Oligomycins / Q000494:pharmacology; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption / Q000187:drug effects; D010545:Peroxides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013367:Submitochondrial Particles / Q000378:metabolism; D013438:Sulfhydryl Compounds; D013772:Tetramethylphenylenediamine / Q000494:pharmacology
D002414:Cations, Monovalent; D003580:Cytochromes; D005609:Free Radicals; D009097:Multienzyme Complexes; D009840:Oligomycins; D010545:Peroxides; D013438:Sulfhydryl Compounds; C031004:oligomycin A; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000968:Antimycin A; D010088:Oxidoreductases; C022691:succinate oxidase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D013772:Tetramethylphenylenediamine; D001585:Benzoyl Peroxide