Figure 1.

P2X₇ Purinoceptors Regulate Mitochondrial Function. P2X₇ purinoceptors are localized in the outer mitochondrial membrane, with the ATP-binding site facing the cytosol. These receptors are coupled with the Complex I by yet unknown cascade; when active, P2X₇ receptors increase the expression and activity of Complex I hence increasing mitochondrial polarization, which leads to an elevation of matrix ionized Ca²⁺ and an increase in ATP production. Genetic deletion of P2X₇ receptors leads to a decrease in Complex I activity and increased NADH/NAD+ ratio with ultimate reduction in ATP production. This is linked to cellular pathology, which underlies the development of dilated cardiomyopathy and possibly to reduced thermogenesis by the brown adipose tissue. This deficiency can be rectified by exogenous methyl-succinate which bypasses Complex I deficiency. Repletion of NAD+ possibly may have similar rescuing effect.