Channel formation by F-ATP synthase and the permeability transition pore: an update

The most recent hypothesis about the nature of the mitochondrial permeability transition is that it forms after a Ca2+-dependent conformational change of the F1FO (F)-ATP synthase. This conformational change would lead to opening of a latent megachannel, which has been extensively characterized in mitoplasts by electrophysiology. Partially purified F-ATP synthases from mammals, yeast and drosophila do form channels with the properties expected of the corresponding permeability transition pores, but the occurrence and molecular mechanism of the transition are debated. Here we discuss the hypothesis that the pore forms from F-ATP synthase based on recent data obtained from genetic manipulation of its subunits