Theoretical evaluation of a possible nature of the outer membrane potential of mitochondria

A possibility of generation of the outer membrane potential in mitochondria has been suggested earlier in the literature, but the potential has not been directly measured yet. Even its nature, metabolic impact and a possible range of magnitudes are not clear, and require further theoretical and experimental analysis. Here, using simple mathematical model, we evaluated a possible contribution of the Donnan and metabolically derived potentials to the outer membrane potential, concluding that the superposition of both is most probable; exclusively Donnan origin of the potential is doubtful because unrealistically high concentrations of charged macromolecules are needed for maintaining its relatively high levels. Regardless of the mechanism(s) of generation, the maximal possible potential seems to be less than 30 mV because significant osmotic gradients, created at higher values, increase the probability of the outer membrane rupture. New experimental approaches for direct or indirect determination of true value of the outer membrane potential are suggested here to avoid a possible interference of the surface electrical potential of the inner membrane, which may change as a result of the extrusion of matrix protons under energization of mitochondria.