An uncoupling channel within the c-subunit ring of the F ₁ F _O ATP synthase is the mitochondrial permeability transition pore

Significance Stressful cellular events cause intracellular Ca 2+ dysregulation, rapid loss of inner mitochondrial membrane potential [the permeability transition (PT)], metabolic dysfunction, and death. Rapid Ca 2+ -induced uncoupling is one of the most important regulators of cell demise. We show that the c-subunit ring of the F 1 F O ATP synthase forms a voltage-sensitive channel, the persistent opening of which leads to PT and cell death. In...