Channel formation by yeast F-ATP synthase and the role of dimerization in the mitochondrial permeability transition

Purified F-ATP synthase dimers of yeast mitochondria display Ca 2+-dependent channel activity with properties resembling those of the permeability transition pore (PTP) of mammals. After treatment with the Ca 2+ ionophore ETH129, which allows electrophoretic Ca2+ uptake, isolated yeast mitochondria undergo inner membrane permeabilization due to PTP opening. Yeast mutant strains ATIM11 and AATP20 (lacking the e and g F-ATP synthase subunits, respectively, which are necessary for dimer formation) display a striking resistance to PTP opening. These results show that the yeast PTP originates from F-ATP synthase and indicate that dimerization is required for pore formation in situ. © 2014 by The American Society for Biochemistry and Molecular Biology.