The central hydrophilic axis of the membrane domain (including E channel) is most likely proton deficient (and hydrated) in the low energy D state. Once an NADH molecule is oxidized (Q is reduced) in the initial turnover cycle(s) starting from the D enzyme, this can lead to partial protonation of the E channel (potentially also other parts of the membranous domain). A minimal proton concentration in the E channel and the central hydrophilic axis of complex I membrane arm is needed to drive fast proton pumping in the A state (Fig. , see also Fig. in and Fig. in ( )), which if not there, proton pumping will not be coupled with the redox activity. This model agrees with the above-described proton pumping proposal (see sections 2 and 6) where protons (green protons in Fig. ) are released to the E channel/central axis due to the Q redox activity.