Role of mitochondrial thiols of different localization in the generation of reactive oxygen species |
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Authors: | T A Fedotcheva N L Shimanovskii A G Kruglov V V Teplova N I Fedotcheva |
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Institution: | 1.Pirogov Russian State Medical University,Moscow,Russia;2.Institute of Theoretical and Experimental Biophysics,Russian Academy of Sciences,Pushchino, Moscow oblast,Russia |
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Abstract: | The role of thiols of the outer and the inner membranes of mitochondria in the regulation of generation of reactive oxygen
species (ROS) has been studied. It was found that N-ethylmaleimide (NEM), which penetrates through the mitochondrial membrane and binds thiols to form thioesters, at concentrations
from 20 to 250 μM activates the production of superoxide anion and hydrogen peroxide during the oxidation of the substrates
of complexes I and II of the respiratory chain. 5′,5′-Dithiobis-(2-nitrobenzoate) (DTNB), which does not penetrate into mitochondria
and binds thiols to form disulfides, weakly activates hydrogen peroxide production during the oxidation of NAD-dependent substrates
and inhibits the ROS production upon succinate oxidation. DTNB is particularly effective in inhibiting the menadione-induced
formation of ROS. The differences in the ROS formation by these reagents are explained by the fact that they influence different
thiol-containing proteins and enzymes. As distinct from NEM, which inhibits complex I of the respiratory chain, DTNB has no
effect on the respiratory chain of mitochondria but can bind the SH-groups of NADH-quinone oxidoreductase, which is localized
in the outer mitochondrial membrane and participates in the redox cycle of menadione. It was also shown that the ability to
inhibit the ADP-stimulated respiration, a feature inherent in both reagents, does not significantly contribute to ROS production. |
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