Bi-stability of the reaction system catalyzed by complex III.

(A) shows the time course of transition of complex III from low to high ROS producing steady state. This transition was triggered in the model by a switch to higher succinate supply (increase in succinate concentration) and it is characterized by the increase of content of semiquinone radical bound at outer (Q_o) site of the complex (SQ) and free ubiquinol (QH₂ free), and decrease ubiquinone content (Q free). Electron transport rate (e_flux) initially increases, but then decreases because the deficit of electron acceptor (Q) impedes the oxidation of cytochrome b_H. As a consequence, cytochrome b_L remains reduced and cannot accept electrons from bound SQ thus increasing SQ content and related ROS production. (B) shows the computed content of semiquinone radicals bound at Qo site of complex III (SQ) and electron flow rates in steady states reached at various succinate supply from an initial state characterized by low SQ content (SQ_l). When the substrate supply overcomes a certain threshold, the system comes to a steady states characterized by the high levels of SQ and ROS production. If the system initially is in one of such high ROS producing states, it evolves to the different steady states after a decrease of succinate supply. Dashed line shows for comparison the continuum of steady states for SQ reached from an initial state characterized by high SQ content (SQ_h). (C) shows the computed content of semiquinone radicals bound at Qo site of complex III (SQ) and electron flow rates in steady states reached at various succinate supply from an initial state characterized by high SQ content (SQ_h). When the substrate supply decreases below a certain threshold, the system comes to a steady states characterized by the low levels of SQ and ROS production. If the system initially is in a one of such low ROS producing states, it evolves to the different steady states after an increase of succinate supply. Dashed line shows for comparison the continuum of steady states for SQ reached from an initial state characterized by low SQ content (SQ_l).