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Biochemistry (Moscow)

, Volume 83, Issue 5, pp 552–561 | Cite as

New Data on Effects of SkQ1 and SkQT1 on Rat Liver Mitochondria and Yeast Cells

  • A. G. Rogov
  • T. N. Goleva
  • T. A. Trendeleva
  • A. P. Ovchenkova
  • D. A. Aliverdieva
  • R. A. ZvyagilskayaEmail author
Article

Abstract

Mitochondria are involved in many processes in eukaryotic cells. They play a central role in energy conservation and participate in cell metabolism and signaling pathways. Mitochondria are the main source of reactive oxygen species, excessive generation of which provokes numerous pathologies and cell death. One of the most promising approaches to the attenuation of oxidative stress in mitochondria is the use of targeted (i.e., transported exclusively into mitochondria) lipophilic cationic antioxidants. These compounds offer advantages over conventional water-soluble antioxidants because they induce the so-called “mild uncoupling” and can prevent collapse of the membrane potential in low, nontoxic concentrations. A novel mitochondria-targeted antioxidant, SkQT1, was synthesized and tested within the framework of the research project guided by V. P. Skulachev. The results of these experiments were initially reported in 2013; however, one publication was not able to accommodate all the data on the SkQT1 interactions with isolated mitochondria and cells. Here, we examined comparative effects of SkQT1 and SkQ1 on rat liver mitochondria (with broader spectrum of energy parame- ters being studied) and yeast cells. SkQT1 was found to be less effective uncoupler, depolarizing agent, inhibitor of respiration and ATP synthesis, and “opener” of a nonspecific pore compared to SkQ1. At the same time SkQ1 exhibited higher antioxidant activity. Both SkQT1 and SkQ1 prevented oxidative stress and mitochondria fragmentation in yeast cells exposed to t-butyl hydroperoxide and promoted cell survival, with SkQT1 being more efficient than SkQ1. Together with the results presented in 2013, our data suggest that SkQT1 is the most promising mitochondria-targeted antioxidant that can be used for preventing various pathologies associated with the oxidative stress in mitochondria.

Keywords

rat liver mitochondria yeast C4R1 SkQ1 SkQT1 respiration membrane potential ATP synthesis Ca2+/Pi-dependent pore oxidative stress cell death 

Abbreviations

Ap5A

P1,P5-di(adenosine-5′)pentaphosphate

CCCP

carbonyl cyanide m-chlorophenylhydrazone

CsA

cyclosporin A

mPTP

mitochondrial permeability transition pore

ROS

reactive oxygen species

SkQ1

10-(6′-plasto-quinonyl)decyltriphenylphosphonium

SkQT1

a mixture of SkQT1(p) and SkQT1(m) in a proportion of 1.4: 1

SkQT1(m)

10-(5′-toluquinonyl)decyltriphenylphosphonium

SkQT1(p)

10-(6′-toluquinonyl)decyltriphenylphosphonium

t-BHP

tert-butyl hydroperoxide

ΔΨ

transmembrane electric potential difference

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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • A. G. Rogov
    • 1
  • T. N. Goleva
    • 1
  • T. A. Trendeleva
    • 1
  • A. P. Ovchenkova
    • 1
  • D. A. Aliverdieva
    • 2
  • R. A. Zvyagilskaya
    • 1
    Email author
  1. 1.Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research CenterRussian Academy of SciencesMoscowRussia
  2. 2.Caspian Institute of Biological ResourcesRussian Academy of SciencesMakhachkalaRussia

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