The chemiosmotic model requires that mitochondrial ATP synthesis and electron flow through the respiratory chain be obligately coupled. requires an intact outer mitochondrial membrane. is supported by the observation that isolated mitochondria that are actively respiring cause the pH of the solution they are in to increase. is supported by the observation that, when isolated mitochondria have an artificial electrochemical gradient (higher pH in the matrix) imposed on them, electrons spontaneously flow through the respiratory chain. The subunits of ATP synthase have three distinct isozymes. are each associated with a subunit. have three distinct conformations. will act as an ATPase if protons flow through the Fo domain into the mitochondrion.