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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1979 Sep;76(9):4340–4344. doi: 10.1073/pnas.76.9.4340

Hydroperoxides can modulate the redox state of pyridine nucleotides and the calcium balance in rat liver mitochondria

Hans Ruedi Lötscher 1, Kaspar H Winterhalter 1, Ernesto Carafoli 1, Christoph Richter 1
PMCID: PMC411570  PMID: 41241

Abstract

When rats are fed a selenium-deficient diet, the glutathione peroxidase activity in liver mitochondria decreases within 5 weeks to 0-6% of that of control animals fed on a diet supplemented with 0.5 ppm of selenium as sodium selenite. Analysis of the temperature dependence of energy-linked Ca2+ uptake by means of Arrhenius plots reveals two breaks (at around 11°C and 24°C) in mitochondria isolated from selenium-supplemented animals, whereas in selenium-deficient rats the break at 11°C is absent. Ca2+-loaded mitochondria of selenium-supplemented rats—i.e., with active glutathione peroxidase in the matrix—lose Ca2+ rapidly, with a concomitant oxidation of endogenous NAD(P)H, when exposed to t-butyl hydroperoxide or H2O2. In contrast, in selenium deficiency, t-butyl hydroperoxide and H2O2 induce neither a release of Ca2+ nor an oxidation of NAD(P)H. The peroxide-induced oxidation of NAD(P)H is reversible in the presence of succinate when no Ca2+ has been taken up. When Ca2+ has previously been accumulated, however, the oxidation of NAD(P)H is irreversible. Enzymatic analysis of mitochondrial pyridine nucleotides reveals that the peroxide-induced oxidation of NAD(P)H in Ca2+-loaded mitochondria leads to a loss of NAD+ and NADP+. It is proposed that the redox state of mitochondrial pyridine nucleotides can be or is in part controlled by glutathione peroxidase and glutathione reductase and is a factor in the balance of Ca2+ between mitochondria and medium.

Keywords: glutathione peroxidase, selenium, calcium release

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Selected References

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