Phenylarsine oxide stimulates pyridine nucleotide-linked Ca2+ release from rat liver mitochondria

Rat liver mitochondria contain a specific Ca2+ release pathway which operates when oxidized mitochondrial pyridine nucleotides are hydrolysed to ADPribose and nicotinamide. Here we report that the hydrophobic bifunctional thiol reagent phenylarsine oxide (PhAsO) at low concentrations stimulates this pathway by promoting a Ca(2+)-dependent hydrolysis of oxidized mitochondrial pyridine nucleotides. Ca2+ release is inhibited by cyclosporine A or m-iodobenzylguanidine, compounds known to prevent intramitochondrial pyridine nucleotide hydrolysis or protein mono(ADPribosyl)ation, respectively. At higher concentrations, PhAsO causes non-specific leakiness of mitochondria.