The effect of a ferric iron complex on isolated rat-liver mitochondria. III. Mechanistic aspects of iron-induced calcium efflux.

Addition of iron(III)-gluconate complex to isolated rat liver mitochondria induced a net efflux of Ca2+ which was not inhibited by ruthenium red. This process resulted in the enhancement of Ca2+ cycling and a consequent membrane potential drop. Under these experimental conditions the content of mitochondrial glutathione did not appear to be critically modified, whereas an extensive oxidation of mitochondrial pyridine nucleotides was parallelly detected. Iron failed to induce appreciable changes in the oxidation level of pyridine nucleotides in mitochondria isolated from rats fed a selenium deficient diet, a condition in which mitochondrial glutathione peroxidase resulted inhibited by 80%. The iron-induced Ca2+ release in Se-deficient mitochondria appeared largely delayed and the membrane potential of these mitochondrial did not present gross alterations. Iron was also found to induce a transient increase in the mitochondrial cyanide-insensitive oxygen consumption. This effect was largely prevented by the addition of the hydrogen peroxide scavenger catalase. It was concluded that iron induced the activation of a specific Ca2+ efflux pathway via the oxidation of pyridine nucleotides due to the hydrogen peroxide metabolism by glutathione enzyme system.