Mitochondrial F-ATP Synthase and Its Transition into an Energy-Dissipating Molecular Machine

Figure 2

The proton circuit across the inner mitochondrial membrane. During the oxidative phosphorylation, the redox reactions of the four respiratory chain complexes are indirectly coupled to ATP synthesis by the F-ATP synthase dimers through the electrochemical proton gradient across the IMM. Return of protons into the matrix independent of ATP synthesis through the basal leak pathway, or through inducible leaks, decreases the electrochemical proton gradient and leads to mitochondrial uncoupling protecting mitochondria against ROS production. Proton back-leaks through the F_O sector of F-ATP synthase, independent of the synthesis of ATP, lead to dissipation of the proton gradient, thus transforming F-ATP synthase into an energy-dissipating structure. Red arrows correspond to proton leaks.