Molecular Regulation of the Mitochondrial F1Fo-ATPsynthase: Physiological and Pathological Significance of the Inhibitory Factor 1 (IF1)

In mammals, the mitochondrial F 1 F o -ATPsynthase sets out the energy homeostasis by producing the bulk of cellular ATP. As for every enzyme, the laws of thermodynamics command it; however, it is privileged to have a dedicated molecular regulator that controls its rotation. This is the so-called ATPase Inhibitory Factor 1 (IF 1 ) that blocks its reversal to avoid the consumption of cellular ATP when the enzyme acts as an ATP hydrolase. Recent evidence has also demonstrated that IF 1 may control the alignment of the enzyme along the mitochondrial inner membrane, thus increasing the interest for the molecule. We conceived this review to outline the fundamental knowledge of the F 1 F o -ATPsynthase and link it to the molecular mechanisms by which IF 1 regulates its way of function, with the ultimate goal to highlight this as an important and possibly unique means to control this indispensable enzyme in both physiological and pathological settings.