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 Ca2+-dependent channel activity with properties resembling those of the permeability transition pore (PTP) of mammals. After treatment with the Ca2+ ionophore ETH129, which allows electrophoretic Ca2+ uptake, isolated yeast mitochondria undergo inner membrane permeabilization due to PTP opening. Yeast mutant strains ΔTIM11 and ΔATP20 (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. Whether channel formation is a general feature of F-ATP synthase dimers across species is unknown. Yeast F-ATP synthase dimers form Ca2+-dependent channels, and the e and g subunits facilitate pore formation in situ through dimerization. F-ATP synthase dimers form the permeability transition pore of yeast. Ca2+-dependent channel formation is a conserved feature of F-ATP synthases.