Molecular mechanisms of transformation of SkQ mitotropic quinones and the search for new approaches to creation of selective free radical traps |
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Authors: | S A Eremeyev V I Kargin K A Motovilov V N Tashlitsky V Yu Markov G A Korshunova N V Sumbatyan M Yu Vyssokikh L S Yaguzhinsky |
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Institution: | 1.Belozersky Institute of Physico-Chemical Biology,Lomonosov Moscow State University,Moscow,Russia |
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Abstract: | Features of the mechanism of action of positively charged benzoquinone derivatives (SkQ), which are the analogs of coenzyme
Q (I), plastoquinone (II), and tocopherol (III), are discussed. It is usually considered that the main target of these compounds
is mitochondria, where they accumulate due to the positive charge of the molecule. In the present work, it is shown with model
systems that the reduced forms of compounds (I–III) under certain conditions can transform into electrically neutral cyclic
zwitterions, which theoretically can escape from the matrix of energized mitochondria against the concentration gradient.
A weak uncoupling effect of molecules I–III has been found on mitochondria. Its existence is in agreement with the abovementioned
transformation of positively charged hydroquinones of type Ia–IIIa into electrically neutral molecules. The data obtained
with model systems suggest that the target of SkQ hydroquinones as free radical traps may be not only mitochondria but also
biochemical systems of the cytoplasm. Due to the presence of a large number of reactive oxygen species (ROS)-dependent signal
systems in a cell, the functioning of cytoplasmic systems might be disturbed under the action of antioxidants. The problem
of selective effect of antioxidants is discussed in detail in the present work, and a functional diagram of selective decrease
of the “background level” of ROS based on differences in the intensity of background and “signal” ROS fluxes is considered. |
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