Quantitative and mechanistic aspects of the hydroperoxide‐induced release of Ca2+ from rat liver mitochondria

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Abstract
In rat liver mitochondria a hydroperoxide-induced hydrolysis of pyridine nucleotides and release of Ca2+ was demonstrated. Pyridine nucleotide hydrolysis and Ca2+ release under conditions of minimized Ca2+ cycling and with smaller Ca2+ loads were investigated. The extent of pyridine nucleotide hydrolysis, measured by pyridine-nucleotide-derived nicotinamide release from intact mitochondria and the Ca2+ release rate show a very similar sigmoidal dependence on the mitochondrial Ca2+ load. The hydrolysis of oxidized pyridine nucleotides is limited under non-cycling conditions. Whereas pyridine nucleotide hydrolysis as measured by nicotinamide release is extensive, net loss of mitochondrial pyridine nucleotides is observed only at relatively high Ca2+ loads. The ability of mitochondria to resynthesize pyridine nucleotides after hydrolysis was indicated. Neither a decrease of reduced, nor an increase of oxidized, mitochondrial glutathione favor Ca2+ release. Apparently, the hydroperoxide-induced Ca2+ release is triggered by a factor which is distal to the oxidation of mitochondrial pyridine nucleotides. Ca2+ release is stimulated when the movement of protons across the inner mitrochondrial membrane is facilitated, giving evidence for the operation of the hydroperoxide-induced release pathway as a Ca2+ H+ antiport.