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Effect of cyanide on mitochondrial membrane depolarization induced by uncouplers

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Abstract

In this work, it was found that the ability of common uncouplers – carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP) and 2,4-dinitrophenol (DNP) – to reduce membrane potential of isolated rat liver mitochondria was diminished in the presence of millimolar concentrations of the known cytochrome c oxidase inhibitor – cyanide. In the experiments, mitochondria were energized by addition of ATP in the presence of rotenone, inhibiting oxidation of endogenous substrates via respiratory complex I. Cyanide also reduced the uncoupling effect of FCCP and DNP on mitochondria energized by succinate in the presence of ferricyanide. Importantly, cyanide did not alter the protonophoric activity of FCCP and DNP in artificial bilayer lipid membranes. The causes of the effect of cyanide on the efficiency of protonophoric uncouplers in mitochondria are considered in the framework of the suggestion that conformational changes of membrane proteins could affect the state of lipids in their vicinity. In particular, changes in local microviscosity and vacuum permittivity could change the efficiency of protonophore-mediated translocation.

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Abbreviations

BLM:

bilayer phospholipid membranes

BSA:

bovine serum albumin

CCCP:

carbonyl cyanide m-chlorophenylhydrazone

DNP:

2,4-dinitrophenol

FCCP:

car-bonyl cyanide p-trifluoromethoxyphenylhydrazone

FCS:

fluo-rescence correlation spectroscopy

MC:

mitochondria

TMRE:

tetramethylrhodamine ethyl ester (dye)

Δψ:

mito-chondrial membrane potential

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Authors and Affiliations

  1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    L. S. Khailova, T. I. Rokitskaya, E. A. Kotova & Y. N. Antonenko

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  1. L. S. Khailova
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  2. T. I. Rokitskaya
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  3. E. A. Kotova
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  4. Y. N. Antonenko
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Correspondence to Y. N. Antonenko.

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Original Russian Text © L. S. Khailova, T. I. Rokitskaya, E. A. Kotova, Y. N. Antonenko, 2017, published in Biokhimiya, 2017, Vol. 82, No. 10, pp. 1489-1496.

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Khailova, L.S., Rokitskaya, T.I., Kotova, E.A. et al. Effect of cyanide on mitochondrial membrane depolarization induced by uncouplers. Biochemistry Moscow 82, 1140–1146 (2017). https://doi.org/10.1134/S0006297917100066

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  • DOI: https://doi.org/10.1134/S0006297917100066

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