Regulation of the mitochondrial ATP synthase/ATPase complex

• Published in: Archives of biochemistry and biophysics Vol. 250; no. 1; pp. 1 - 18
• Main Authors: Schwerzmann, Klaus, Pedersen, Peter L.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.10.1986; Elsevier
• Subjects: Animals; Applied sciences; ATPase Inhibitory Protein; Binding Sites; Electron Transport; Exact sciences and technology; Mitochondria - enzymology; Models, Chemical; Other techniques and industries; Protein Binding; Proteins - physiology; Proton-Translocating ATPases - antagonists & inhibitors; Proton-Translocating ATPases - metabolism
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/0003-9861(86)90695-8

The mitochondrial ATP synthase/ATPase (F 0F 1 ATPase) is perhaps the most complex enzyme known. In animal systems it consists of a minimum of 11 different polypeptide chains, 10 (or more) of which appear to be essential for function, and 1 called the “ATPase inhibitor peptide” which is involved in regulation. Recent studies from a variety of laboratories indicate that the ATP synthase/ATPase complex is regulated by several interrelated factors including (a) the thermodynamic poise of the proton gradient across the inner mitochondrial membrane; (b) the ATPase inhibitor peptide; (c) ADP (and/or ADP and P i); (d) divalent cations; and perhaps (e) the redox state of SH groups on the F 1 molecule. The central focus of this review is the ATPase inhibitor peptide. A model involving four distinct conformational states of F 1 seems essential to account for the inhibitor's mode of action. The model depicts the ATPase inhibitor protein as acting at the asymmetric center of the F 1 moiety. In addition, it accounts for the “unidirectional” role of the inhibitor peptide as a “down regulator” of ATP hydrolysis and for its binding/debinding dependence on the proton motive force and other regulatory factors. Finally, it is suggested that during any physiological process, where there is an energy demand followed by a resting phase, the F 1 molecule may follow a “cyclic” path involving the four distinct conformational states of the enzyme.