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

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.

• glutathione peroxidase
• selenium
• calcium release