Molecular Regulation of the Mitochondrial F1Fo-ATPsynthase: Physiological and Pathological Significance of the Inhibitory Factor 1 (IF
1
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Figure 1
Oxidative phosphorylation and the mammalian F1Fo-ATPsynthase. (a) Scheme of the mitochondrial OXPHOS: it is composed of five complexes, which couple the generation of a proton motive force through the mitochondrial inner membrane (IMM) with ATP synthesis. The first four complexes form the electron-transport chain (ETC), which catalyses the oxidation of NADH and FADH2 to NAD+ and FAD respectively, with the associated reduction of molecular oxygen, to which electrons are transferred, to water. During the process, protons are translocated against a gradient in the intermembrane space by complexes I, III, and IV; the generation of a proton electrochemical potential (), also called proton motive force (pmf), is achieved, driving the ATP synthesis, which is catalyzed as the final step by the F1Fo-ATP synthase (Complex V). The supramolecular organization of the respiratory chain, with the F1Fo-ATPsynthase localized to mitochondrial cristae, where a higher surface density of protons is realized, allows a better enzymatic performance of complex V. (b) Diagram of the structure of mammalian F1Fo-ATPsynthase. We can divide the enzymatic complex into 4 principal subdomains: a catalytic headpiece (), hosting the three catalytic sites for ATP synthesis (one in each subunit), a proton channel () and two stalks, the central rotor () and the peripheral stator ((F6)OSCP) that link the first two subdomains together. While protons flow through the Fo channel from the intermembrane space into the matrix, a rotation of the stator inside the catalytic headpiece is induced, allowing a cyclic change in -subunits conformation and the synthesis of ATP (N.B. Subunits A6L, , , and are omitted in the scheme).