title: Cooperativity and flexibility of the protonmotive activity of mitochondrial respiratory chain.
abstract: Functional and structural data are reviewed which provide evidence that proton pumping in cytochrome c oxidase is associated with extended allosteric cooperativity involving the four redox centers in the enzyme . Data are also summarized showing that the H+/e- stoichiometry for proton pumping in the cytochrome span of the mitochondrial respiratory chain is flexible. The DeltapH component of the bulk-phase membrane electrochemical proton gradient exerts a decoupling effect on the proton pump of both the bc1 complex and cytochrome c oxidase. A slip in the pumping efficiency of the latter is also caused by high electron pressure. The mechanistic and physiological implications of proton-pump slips are examined. The easiness with which bulk phase DeltapH causes, at least above a threshold level, decoupling of proton pumping indicates that for active oxidative phosphorylation efficient protonic coupling between redox complexes and ATP synthase takes place at the membrane surface, likely in cristae, without significant formation of delocalized DeltamuH+. A role of slips in modulating oxygen free radical production by the respiratory chain and the mitochondrial pathway of apoptosis is discussed.
authors.affiliation: Department of Medical Biochemistry, Biology and Physics, University of Bari, Policlinico, P.zza G. Cesare, 70124 Bari, Italy. papabchm@cimedoc.uniba.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
authors.forename: Michele
authors.initials: M
authors.lastname: Lorusso
authors.forename: Marco
authors.initials: M
authors.lastname: Di Paola
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001692:Biological Transport; D019069:Cell Respiration; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000502:physiology*; D003576:Electron Transport Complex IV / Q000502:physiology*; D006801:Humans; D051336:Mitochondrial Membranes / Q000502:physiology*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D017494:Proton Pumps / Q000502:physiology; D018892:Proton-Motive Force; D006180:Proton-Translocating ATPases / Q000502:physiology; D011522:Protons; D013367:Submitochondrial Particles / Q000502:physiology
chemical_list: D017494:Proton Pumps; D011522:Protons; D003576:Electron Transport Complex IV; D006180:Proton-Translocating ATPases; D014450:Electron Transport Complex III