L. G. Babich*, S. G. Shlykov, A. I. Panchenko, S. O. Kosterin

Department of Muscle Biochemistry, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
*e-mail: babich@biochem.kiev.ua

Received: 16 September 2025; Revised: 21 October 2025;
Accepted: 30 January 2026; Available on-line: 23 February 2026

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