Extramitochondrial ATP modulates Са(2+) signaling in myometrial mitochondria

It was postulated that mitochondria are sensors and effectors of ATP synthesis. Our results suggest that ATP may play a role as an intracellular signaling molecule. We have shown that the baseline Ca2+ concentration in the mitochondrial matrix increased in the presence of ATP or MgATP in the incubation media of isolated mitochondria. Activation or inhibition of both the respiration and Ca2+ uniporter activity, as well as the removal of Mg2+ from the incubation medium, or addition of A438079, an antagonist of plasma membrane P2X7 receptors, followed by the addition of ATP did not affect the ATP-induced increase of matrix baseline Ca2+ concentration. These results showed that extramitochondrial ATP modulates Ca2+ signaling in mitochondria independently of the Ca2+ uniporter and the respiratory chain activity. In the presence of UTP or MgUTP instead of ATP or MgATP, an increase of the matrix baseline Ca2+ concentration was not observed indicating that the studied effects are selective for ATP. Keywords: A438079, ATP, Ca2+ concentration, matrix, Mg(2+), mitochondria, Ru360, spermine, UTP