کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1942674 | 1052623 | 2011 | 11 صفحه PDF | دانلود رایگان |

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 (ΔΨm) and the proton (ΔpHm) gradient, displayed a similar effect. Quantitative estimation of the ΔΨm 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 200–210 mV 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 bc1 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.
Research highlights
► MCA of mitochondrial respiration was applied to permeabilized cells.
► The mitochondrial protonmotive force depresses the flux control coefficient of COX.
► A narrow threshold range of the ΔΨmt accounts for its effect on COX.
► The respiratory flux controls of CI and CIII but not of CII respond as CIV to ΔΨmt.
Journal: Biochimica et Biophysica Acta (BBA) - Bioenergetics - Volume 1807, Issue 9, September 2011, Pages 1114–1124