Inhibition by purine nucleotides of the release of reactive oxygen species from muscle mitochondria: Indication for a function of uncoupling proteins as superoxide anion transporters

► GDP and GTP decrease release of reactive oxygen species from muscle mitochondria. ► The release of superoxide anion rather than that of hydrogen peroxide is inhibited. ► GTP increases accumulation of reactive oxygen species within mitochondrial matrix. ► Uncoupling proteins may function as mitochondrial carriers of the superoxide anion. Release of reactive oxygen species (ROS), measured as the sum of hydrogen peroxide (H2O2) and superoxide anion radical (O2-), from respiring rat heart and skeletal muscle mitochondria was significantly decreased by millimolar concentrations of GTP or GDP. Attempts to differentiate between the two forms of ROS showed that the release of O2- rather than that of H2O2 was affected. Meanwhile, intramitochondrial ROS accumulation, measured by inactivation of aconitase, increased. These results suggest that guanine nucleotides inhibit the release of O2- from mitochondria. As these nucleotides are known inhibitors of uncoupling proteins (UCPs), it is proposed that UCPs may function as carriers of O2-, thus enabling its removal from the matrix compartment.