Opposite and tissue-specific effects of coenzyme Q2 on mPTP opening and ROS production between heart and liver mitochondria: Role of complex I

Coenzyme Q2 (CoQ2) is known to inhibit mitochondrial permeability transition pore (mPTP) opening in isolated rat liver mitochondria. In this study, we investigated and compared the effects of CoQ2 on mPTP opening and ROS production in isolated rabbit heart and rat liver mitochondria. Mitochondria were isolated from New Zealand White rabbit hearts and Wistar rat livers. Oxygen consumption, Ca2 +-induced mPTP opening, ROS production and NADH DUb-reductase activity were measured. Rotenone was used to investigate the effect of CoQ2 on respiratory complex I activity. CoQ2 (23 μM) reduced the respiratory control index by 32% and 57% (p < 0.01) in heart and liver mitochondria respectively, mainly through an increased oxygen consumption in state 4. CoQ2 induced a 60% (p < 0.05) decrease of calcium retention capacity (CRC) in heart mitochondria and inversely a 46% (p < 0.05) increase in liver mitochondria. In basal condition, CoQ2 induced a 170% (p < 0.05) increase of H2O2 production in heart mitochondria and 21% (ns) decrease of H2O2 production in liver mitochondria. Because rotenone, a complex I inhibitor, increases H2O2 production in heart but not in liver mitochondria we investigated the CoQ2 effect in a dose–response assay of complex I inhibition by rotenone in both mitochondria. CoQ2 antagonized the effect of rotenone on respiratory complex I activity in liver but not in heart mitochondria. CoQ2 significantly reduced NADH DUb-reductase activity in liver (− 47%) and heart (− 37%) mitochondria. In conclusion, our data showed that on the contrary to what was observed in liver mitochondria, CoQ2 favors mPTP opening and ROS production in heart mitochondria through an opposite effect on respiratory complex I activity.

► CoQ2 has opposite effects on mPTP opening in heart's and liver's mitochondria.
► CoQ2 inhibits NADH-reductase activity in heart's and liver's mitochondria.
► CoQ2 antagonizes rotenone-inhibition of complex I in liver's mitochondria.
► CoQ2 doesn't antagonize rotenone-inhibition of complex I in heart's mitochondria.
► CoQ2 effect on mPTP is tissue dependent and in relation with complex I activity.