The Bifurcation of Electrons in the Bc1 Complex and the Antimycin Inhibition
Résumé
A stochastic approach based on the Gillespie algorithm is particularly well suited to describe the time course of redox reactions that occur within respiratory chain complexes. Indeed, these reactions involve the movement of few electrons between individual redox centers of a given unique complex and not populations of electrons and redox centers as considered in modeling with ordinary differential equations. Using a stochastic simulation without any other assumptions, we recently demonstrated the natural emergence of an electron bifurcation at the Qo site of the bc1 complex, with few short circuits and a very short residence time of the semiquinone in the Qo site and therefore little generation of ROS under normal operating conditions in accordance with the modified Q-cycle mechanism. The model also accounts for the antimycin inhibition and the accompanying increase in ROS production. The antimycin inhibition is mainly because the electron on heme bL cannot return on the negative semiquinone SQ● -. We obtain a sigmoïd inhibition by antimycin due to the fact that when only one antimycin is bound per bc1 dimer, the electron of the inhibited monomer systematically crosses the dimer interface from bL to bL to reduce a quinone or a semiquinone species in the other (free) Qi site. Because this step is not limiting, the activity is unchanged when compared to the activity of the free dimer (free of antimycin). Interestingly, this bL–bL pathway is almost exclusively taken in this half-bound antimycin dimer. In the free dimer, the natural faster pathway is bL–bH on the same monomer. The addition of the assumption of half-of the-sites reactivity to the previous hypothesis leads to a transient activation in the antimycin titration curve preceding a quasi-complete inhibition at antimycin saturation as experimentaly observed in some cases. We are extended our simulations with the incorporation of protons release or uptake in the electron model.