The IF(1) inhibitor protein of the mitochondrial F(1)F(0)-ATPase.
Recent studies on the IF(1) inhibitor protein of the mitochondrial F(1)F(0)-ATPase from molecular biochemistry to possible pathophysiological roles are reviewed. The apparent mechanism of IF(1) inhibition of F(1)F(0)-ATPase activity and the biophysical conditions that influence IF(1) activity are summarized. The amino acid sequences of human, bovine, rat and murine IF(1) are compared and domains and residues implicated in IF(1) function examined. Defining the minimal inhibitory sequence of IF(1) and the role of conserved histidines and conformational changes using peptides or recombinant IF(1) is reviewed. Luft's disease, a mitochondrial myopathy where IF(1) is absent, is described with respect to IF(1) relevance to mitochondrial bioenergetics and clinical observations. The possible pathophysiological role of IF(1) in conserving ATP under conditions where cells experience oxygen deprivation (tumor growth, myocardial ischemia) is evaluated. Finally, studies attempting to correlate IF(1) activity to ATP conservation in myocardial ischemic preconditioning are compared.
Green
D W
DW
3-Dimensional Pharmaceuticals, Inc., Exton, PA 19341, USA. green@3dp.com
Grover
G J
GJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008929:Mitochondria, Heart / Q000201:enzymology*; D017240:Mitochondrial Myopathies / Q000235:genetics; D008969:Molecular Sequence Data; D017202:Myocardial Ischemia / Q000503:physiopathology; D011487:Protein Conformation; D011506:Proteins / Q000494:pharmacology*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D017386:Sequence Homology, Amino Acid; D000097795:ATPase Inhibitory Protein
D000255:Adenosine Triphosphate; D004791:Enzyme Inhibitors; D011506:Proteins; D006180:Proton-Translocating ATPases; D000097795:ATPase Inhibitory Protein