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Studies on Mitochondria Directed Plastoquinones

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Mitochondrial Biology and Experimental Therapeutics

Abstract

Mitochondria-targeted cationic plastoquinone derivatives (SkQs, e.g. SkQ1, SkQR1) and their analogs lacking plastoquinol moiety (C12TPP, C12R1) can pass through bilayer phospholipid membrane. Their cationic forms are accumulated in isolated mitochondria or in mitochondria of living cells, driven by membrane potential. These compounds were extensively tested in model lipid membranes, isolated mitochondria and in living human cells in culture. It was found that SkQs are antioxidants that quench reactive oxygen species (ROS) in mitochondria, and mild uncouplers that facilitate transmembrane proton transport by fatty acids. Both properties result in efficient prevention of oxidative stress and protection of mitochondria and cells from damage by ROS, making SkQs a promising drug candidate against pathologies caused by excess mitochondrial ROS generation. Recent discovery of SkQ1 antibacterial activity at concentrations not toxic to human cells opens a perspective for development of new antibiotics. In this chapter, we summarize recent in vitro experiments with mitochondria-targeted plastoquinones.

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Abbreviations

MitoQ:

10-(6′-Ubiquinonyl) decyltriphenylphosphonium

MPC:

membranophilic penetrating cation

MPI:

membranophilic penetrating ion

PQ:

Plastoquinone

ROS:

Reactive oxygen species

SkQ:

Cationic derivative of plastoquinone or methyl plastoquinone

SkQ1:

10-(6′-Plastoquinonyl) decyltriphenylphosphonium

SkQ2M:

10-(6′-Plastoquinonyl) decylmethylcarnitine

SkQ3:

10-(6′-Methylplastoquinonyl) decyltriphenylphosphonium

SkQ4:

10-(6′-Plastoquinonyl) decyltributylammonium

SkQ5:

5-(6′-Plastoquinonyl) amyltriphenylphosphonium

SkQR1:

10(Plastoquinonyl) decylrhodamine 19

TPB:

Tetraphenylborate

TPP:

Tetraphenylphosphonium

Δψ :

Transmembrane electric potential difference

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Acknowledgements

This work was supported by the Russian Science Foundation (Project No. 14-50-00029 (B.A.F.) and Project No. 14–24-00107 (V.P.S.)).

Conflict of Interest V.P.S. is a board member of Mitotech LLC, a biotech company which owns rights for compounds of SkQ type.

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Authors and Affiliations

  1. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia

    Boris A. Feniouk & Vladimir P. Skulachev

  2. A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia

    Boris A. Feniouk & Vladimir P. Skulachev

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  1. Boris A. Feniouk
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  2. Vladimir P. Skulachev
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Correspondence to Vladimir P. Skulachev .

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  1. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Paulo J. Oliveira

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Feniouk, B.A., Skulachev, V.P. (2018). Studies on Mitochondria Directed Plastoquinones. In: Oliveira, P. (eds) Mitochondrial Biology and Experimental Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-73344-9_23

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