Hysteresis and bistability in the succinate-CoQ reductase activity and reactive oxygen species production in the mitochondrial respiratory complex II

In order to account for activation of Complex II by succinate in the forward succinate-quinone oxidoreductase direction, we developed and analyzed a computational mechanistic model of electron transfer and reactive oxygen species formation in CII

Nikolay I. Markevich; Miliausha H. Galimova; Lubov N. Markevich

2020

Scholarcy highlights

  • In order to account for activation of Complex II by succinate in the forward succinate-quinone oxidoreductase direction, we developed and analyzed a computational mechanistic model of electron transfer and reactive oxygen species formation in CII
  • CII reversibly oxidizes succinate to fumarate in the tricarboxylic acid cycle and transfers the electrons, produced by this reaction to the membrane quinone pool, providing ubiquinol QH2 to electron transport chain
  • In order to account for activation of CII by succinate in the forward SQR direction, we developed and analyzed a computational mechanistic model of electron transfer and ROS formation in CII
  • It was found that re-binding of succinate to the unoccupied dicarboxylate binding site when FAD is reduced with subsequent oxidation of FADH2 creates a positive feedback loop in the succinate oxidation
  • The model predicts that this positive feedback can result in hysteresis and bistable switches in SQR activity and ROS production in CII
  • In the presence of hysteresis with two stable branches with high and low SQR activity, high SQR activity is maintained even with a very strong drop in the succinate concentration, which may be necessary in the process of cell functioning in stressful situations
  • A high stationary rate of reactive oxygen species production in Complex II can be maintained at low succinate concentrations

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