Localized proton circuit

The mechanism of ATP synthesis discussed here assumes that protons extruded during electron transport are in the bulk phase surrounding the inner mitochondrial membrane (intermembrane and extramitochondrial spaces). An alternative view is that there are local proton circuits within or close to the respiratory chain and complex V, and that these protons may not be in free equilibrium with the bulk phase (Williams, 1978), although this has not been supported experimentally (for references see Nicholls and Ferguson, 1992). The chemiosmotic mechanism is both elegant and simple and explains all the known facts about ATP synthesis and its dependence on the structural integrity of the mitochondria, although the details may appear complex. This mechanism will now be discussed in more detail. 

Before considering this information in detail, it is worthwhile to summarize briefly the implications of a localized proton circuit. One possibility is that the major part of the proton current flows not through the bulk aqueous phase (Fig. 2.6a) but along the two surfaces of the membrane (Fig. 2.6b). Note that in this model there is no insulating barrier between the surfaces of the membrane and the bulk phases. Therefore, under steady-state conditions, the electrochemical potential of the protons on the surfaces of the membrane must be the same as in the bulk phases, since otherwise there would be a net flow of protons down the supposed gradient from surface to bulk. This model does not therefore represent true localized chemiosmosis, since the bulk-phase potential measured experimentally will accurately reflect the true potential driving ATP synthesis. 

With these observations in mind we shall now consider the nature of the thermodynamic and kinetic discrepancies which have led a number of groups to consider the possibility of localized proton circuits. 

These discrepancies could be due to experimental problems in the measurement of the potentials, or to the existence of micro-circuits out of equilibrium with the bulk phases. These would possess a significant resistance between the localized proton circuit and the bulk phase. The respiratory chain would see the localized... 

Fig. 2.6. Hypothetical localized variants on the proton circuit, a, fully delocalized circuit b, proton current flows along surface of membranes (note that circuit is still in equilibrium with the bulk phases) c, one leg of the proton circuit is conducted through a lateral channel insulated from the bulk phase d, both legs of the proton circuit are conducted through lateral channel insulated from the bulk phases R, respiratory chain A, ATP synthase. Note the necessity for both outward and return legs in all models.

The next stage in developing a model of localized chemiosmosis is to assume that there is a substantial resistance between the local circuit and the bulk phase [43,44]. One could devise hypothetical models in which one (Fig. 2.6c) or both (Fig. 2.6d) of the portions of the proton circuit parallel to the membrane were insulated from the bulk phases. It is important, however, to appreciate that such models still require the presence of a highly insulating phase separating the outward and return limbs of the proton circuit, with the addition of one or two further substantial resistances to protons. 

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