Impact of exercise training on mitochondrial dynamics during ischemia-reperfusion

Abstract

Mitochondrial fission is a key trigger of cardiac ischemia-reperfusion injuries (IR) injuries. Despite exercise training (ExTr) is known as an efficient strategy to protect the heart, its impact on the dynamic of the mitochondrial network remain to be investigated. To evaluate the impact of ExTr on the process of mitochondrial fission during IR. Isolated hearts from ExTr or Sedentary (Sed) rats were subjected to IR. Hearts samples were collected after 10 min of reperfusion for biochemical assays or electron microscopic analysis. Finally, DHR123 was used to detect ROS production on isolated cardiomyocytes treated or not with the mitochondrial fission inhibitor Mdivi1. We confirmed on isolated rat hearts that ExTr reduced heart sensitivity to IR. This was associated with lower ROS production evaluated by DHE fluorescence and higher mitochondria Ca2+ retention capacities. We next confirmed that IR was associated with mitochondrial fission as well as the translocation and activation of the Dynamin related protein 1 (Drp1), known as the central regulator of mitochondrial fission. Interestingly, ExTr limited both the activation of Drp1 and the fission of mitochondria. We also reported that ExTr tended to increase the level of Mfn2, known as a central regulator of mitochondrial fusion. Finally, on isolated cardiomyocytes stimulated with H2O2 to mimic IR, we reported that Mdivi1 impact the level of ROS production only in Sed cells. This confirms that mitochondrial fission was more pronounced in Sed cells and contributes to increased ROS production during IR. Altogether, our results support the hypothesis that ExTr is able to modulate the dynamic of the mitochondrial network during IR, which could participate to exercise-induced cardioprotection.