Kaila and colleagues, by performing multiscale computer simulations, have proposed a coupling model in which QH2 formed after two-electron reduction and local protonation (at site 1) diffuses to a second site within the Q tunnel . The presence of a second Q binding site within the Q tunnel is supported by both structural and simulation data (see section 3). The localization of QH2 at the second site and the pKa changes caused by two proton holes on the conserved residues of the NDUFS2 subunit (see section 5) trigger proton pumping in the membrane arm of complex I. According to their model, which satisfies the reversibility of complex I, each antiporter-like subunit picks up one proton from the N side, and releases to the P side in coupling with the dynamics of conserved charged pairs (Lys/Glu), that undergo conformational change due to change in protonation patterns of titratable residues in the neighboring subunits. Recently, the mechanism has been modified where in addition to the binding of QH2 at the second site, it is the release of the proton upon QH2 deprotonation towards the E channel and the membrane domain of complex I that causes proton pumping . Importantly, there is no inter-antiporter proton transfer in their mechanism because of the higher energy barriers obtained from computations. However, recent computations have suggested that proton transfer between antiporter-like subunits can occur with reasonable thermodynamics and kinetics (see section 9). This is in agreement with several recent high resolution structures revealing bridging water molecules between antiporter-like subunits , which can catalyze proton transfer. An experimental resolution to the question of whether antiporter-like subunits can exchange protons between them will help in solving the proton pumping mechanism of complex I.