title: Variation of flux control coefficient of cytochrome c oxidase and of the other respiratory chain complexes at different values of protonmotive force occurs by a threshold mechanism.
abstract: The metabolic control analysis was applied to digitonin-permeabilized HepG2 cell line to assess the flux control exerted by cytochrome c oxidase on the mitochondrial respiration. Experimental conditions eliciting different energy/respiratory states in mitochondria were settled. The results obtained show that the mitochondrial electrochemical potential accompanies a depressing effect on the control coefficient exhibited by the cytochrome c oxidase. Both the components of the protonmotive force, i.e. the voltage (ΔΨ(m)) and the proton (ΔpH(m)) gradient, displayed a similar effect. Quantitative estimation of the ΔΨ(m) unveiled that the voltage-dependent effect on the control coefficient of cytochrome c oxidase takes place sharply in a narrow range of membrane potential from 170-180 to 200-210mV consistent with the physiologic transition from state 3 to state 4 of respiration. Extension of the metabolic flux control analysis to the NADH dehydrogenase and bc(1) complexes of the mitochondrial respiratory chain resulted in a similar effect. A mechanistic model is put forward whereby the respiratory chain complexes are proposed to exist in a voltage-mediated threshold-controlled dynamic equilibrium between supercomplexed and isolated states.
authors.affiliation: Department of Biomedical Sciences, University of Foggia, Italy. quarato@sciences.sdsu.edu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarato
authors.forename: Claudia
authors.initials: C
authors.lastname: Piccoli
authors.forename: Rosella
authors.initials: R
authors.lastname: Scrima
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Capitanio
mesh_terms: D045744:Cell Line, Tumor; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D011522:Protons
chemical_list: D011522:Protons; D003576:Electron Transport Complex IV