The metabolism of menadione impairs the ability of rat liver mitochondria to take up and retain calcium.
The ability of mitochondria to take up and retain Ca2+, and thereby to effect the free intracellular concentration of this ion, is well established. More recently, it has been reported (Lehninger, A. L., Vercesi, A., and Bababunmi, E. A. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 1690-1696) that the redox state of pyridine nucleotides modulates mitochondrial Ca2+ balance, since the oxidation of mitochondrial NAD(P)H is associated with the release of Ca2+ from these organelles. The latter may be achieved by a variety of treatments including the incubation of Ca2+-loaded liver mitochondria with hydroperoxides, the metabolism of which by the glutathione peroxidase-glutathione reductase system results in NADPH consumption. The metabolism of menadione (2-methyl-1,4-naphthoquinone) by Ca2+-loaded rat liver mitochondria results in rapid oxidation and loss of pyridine nucleotides and a decrease in ATP level. It is also associated with Ca2+ release and an impaired ability of the mitochondria to take up and retain Ca2+. The effects of menadione on mitochondrial Ca2+ balance are more rapid and pronounced than those of t-butylhydroperoxide, and in contrast to those observed with the hydroperoxide, they are not abolished by pretreatment with a glutathione-depleting agent. The effects of menadione on Ca2+ homeostasis are probably initiated by NAD(P)H oxidation linked to the reduction of menadione by both NADH-ubiquinone oxidoreductase and NAD(P)H:(quinone-acceptor) oxidoreductase.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D014812:Vitamin K / Q000378:metabolism* / Q000494:pharmacology
D009243:NAD; D014812:Vitamin K; D009249:NADP; D002118:Calcium