Fig. 6

Schematic model of promoting PKM2 tetramerization alleviates the decompensation of cardiac function by regulating oxidative stress and mitochondrial dynamics. Pressure overloading induces cardiomyocyte hypertrophy with upregulated PKM2 level, and the tetrameric proportion of PKM2 is reduced by intracellular oxidative stress. An imbalanced ratio of PKM2 tetramer/monomer upregulates Drp1 level and increases OPA1 cleavage, and ultimately leads to mitochondria disorganization and elevated ROS level. This vicious cycle eventually accelerates the apoptosis of cardiomyocytes and promotes cardiac function into the decompensated phase. The application of TEPP-46 can improve mitochondrial network formation, mitigates oxidative stress and alleviates the decompensation of cardiac function via enhancing PKM2 tetramer formation