The molecular mechanism of respiratory complex I remains yet to be fully determined. However, there are some common general principles that have started to emerge from structural and computational data. For instance, the presence of multiple Q binding sites in the Q tunnel, and the linkage between the distal Q binding sites and the membrane arm of complex I via the E channel. However, the number and position of P side pathways and details of proton movements still need to be elucidated by future work. In the framework of proton pumping models involving a single Q substrate, a model of redox-coupled proton pumping is discussed, which satisfies most experimental and theoretical constraints. In the light of available biochemical, structural and simulation data, it is proposed that the exergonic protonation of anionic species drive uphill proton transfer to the P side of the bioenergetic membrane.