The IF1 inhibitor protein of the mitochondrial F1F0-ATPase

AbstractRecent studies on the IF1 inhibitor protein of the mitochondrial F1F0-ATPase from molecular biochemistry to possible pathophysiological roles are reviewed. The apparent mechanism of IF1 inhibition of F1F0-ATPase activity and the biophysical conditions that influence IF1 activity are summarized. The amino acid sequences of human, bovine, rat and murine IF1 are compared and domains and residues implicated in IF1 function examined. Defining the minimal inhibitory sequence of IF1 and the role of conserved histidines and conformational changes using peptides or recombinant IF1 is reviewed. Luft’s disease, a mitochondrial myopathy where IF1 is absent, is described with respect to IF1 relevance to mitochondrial bioenergetics and clinical observations. The possible pathophysiological role of IF1 in conserving ATP under conditions where cells experience oxygen deprivation (tumor growth, myocardial ischemia) is evaluated. Finally, studies attempting to correlate IF1 activity to ATP conservation in myocardial ischemic preconditioning are compared