Menadione (2-methyl-1,4-naphthoquinone)-induced Ca2+ release from rat-liver mitochondria is caused by NAD(P)H oxidation.
Incubation of rat-liver mitochondria with menadione in the presence of succinate and rotenone resulted in rapid glutathione and NAD(P)H oxidation followed by Ca2+ release and mitochondrial swelling. Ca2+ release, NAD(P)H oxidation and mitochondrial swelling, were also observed in mitochondria from selenium-deficient rats. Glutathione was only slowly oxidized, suggesting that glutathione oxidation, and subsequent NAD(P)H oxidation via the glutathione peroxidase-glutathione reductase system were not required for Ca2+ release by menadione. Isocitrate prevented and reversed Ca2+ release dose-dependently but dicoumarol had no effect indicating that NADH-ubiquinone oxidoreductase and not DT-diaphorase was responsible for NAD(P)H oxidation. Superoxide anion radical was formed by cyanide-resistant respiration, suggesting that menadione undergoes a one-electron reduction to an autoxidizable semiquinone radical by NADH-ubiquinone oxidoreductase. The inability of menadione to oxidize glutathione in selenium-deficient mitochondria indicates that the metabolism of the superoxide dismutation product, H2O2, by glutathione peroxidase was probably responsible for the glutathione oxidation in selenium-replete mitochondria.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism; D014812:Vitamin K / Q000494:pharmacology* / Q000633:toxicity
D013481:Superoxides; D014812:Vitamin K; D009249:NADP; D005978:Glutathione; D002118:Calcium