FIGURE 6.

Q-cycle model. The mechanism of superoxide formation in complex III (bcl1 complex). The reaction starts from the oxidation of the CoQ quinol (QH₂) in a bifurcated electron transfer reaction at the Q_o site of the complex III. The first electron is transferred to a high reduction potential chain consisting of the iron-sulfur protein (ISP, aka Rieske protein), cytochrome c₁ (cyt c₁), cytochrome c (cyt c), and further to cytochrome c oxidase (not shown). The remaining semiquinone (Q_o−·) is unstable. It donates the second electron to the low reduction potential chain consisting of two cytochromes b, cyt b_L and cyt b_H, which serve as a pathway conducting electrons to the Q_i site. There these electrons reduce another CoQ molecule. To provide two electrons required for the complete reduction of CoQ quinone at the Q_i-site, the Q_o-site oxidizes two QH₂ molecules in two successive steps. The first electron at the Q_i-site generates a stable semiquinone (Q_i−) that is reduced to a quinol (QH₂) by the second electron. Most frequently used inhibitors of complex III, stigmatellin and myxothiazol, prevent the transfer of the first electron to ISP and the binding of the quinol at the Q_o site correspondingly. [Modified from Starkov and Fiskum (418), with permission from Elsevier.]