Q-cycle in the inner mitochondrial membrane of S. cerevisiae. (1) Reduction of CoQ by two electrons coming from a noncoupled NADH-CoQ reductase and heme b H, followed by consumption of 2H+ from mitochondrial matrix. This occurs near the inner surface of the inner mitochondrial membrane (center i). (2) Diffusion of CoQH2 from center i to center o localized near the outer membrane surface. (3) One-electron oxidation of CoQH2 by the nonheme FeS cluster of Complex III (FeSIII). Here, reduced FeSIII and anion-radical CoQ∓ are formed. 2H+ are released to the intermembrane space. (3a) FeSIII is oxidized resulting in an electron transfer to O2 via cytochromes c 1, c, and cytochrome oxidase, which forms H2O. (4) CoQ∓ oxidation by heme b L. (4a) Alternatively, CoQ∓ can be oxidized by O2 in a O2 ∓-generating fashion. (5) Transmembrane electron transfer from b L to b H. (6) The CoQ diffusion back to center i. Operation of Q-cycle results in generation of ΔΨ and ΔpH (matrix being negatively charged and alkalinized). ΔΨ inhibits the b L → b H electron transfer and, hence, stimulates alternative CoQ∓ oxidation by O2 and generation of O2 ∓. Uncoupler discharges ΔΨ by passive H+ influx from the intermembrane space to matrix and, as a result, inhibits the ROS generation. Myxothiazol (myxo) also suppresses ROS generation by preventing CoQH2 oxidation to CoQ∓ in center o. As for antimycin A (anti), it stimulates ROS production by inhibiting oxidation of b H and, as a consequence, of b L.