Biochemistry (Moscow)

, Volume 80, Issue 12, pp 1589–1597 | Cite as

Uncoupling and toxic action of alkyltriphenylphosphonium cations on mitochondria and the bacterium Bacillus subtilis as a function of alkyl chain length

  • L. S. Khailova
  • P. A. Nazarov
  • N. V. Sumbatyan
  • G. A. Korshunova
  • T. I. Rokitskaya
  • V. I. Dedukhova
  • Yu. N. Antonenko
  • V. P. Skulachev
Article

Abstract

A series of permeating cations based on alkyl derivatives of triphenylphosphonium (Cn-TPP+) containing linear hydrocarbon chains (butyl, octyl, decyl, and dodecyl) was investigated in systems of isolated mitochondria, bacteria, and liposomes. In contrast to some derivatives (esters) of rhodamine-19, wherein butyl rhodamine possessed the maximum activity, in the case of Cn-TPP a stimulatory effect on mitochondrial respiration steadily increased with growing length of the alkyl radical. Tetraphenylphosphonium and butyl-TPP+ at a dose of several hundred micromoles exhibited an uncoupling effect, which might be related to interaction between Cn-TPP+ and endogenous fatty acids and induction of their own cyclic transfer, resulting in transport of protons across the mitochondrial membrane. Such a mechanism was investigated by measuring efflux of carboxyfluorescein from liposomes influenced by Cn-TPP+. Experiments with bacteria demonstrated that dodecyl-TPP+, decyl-TPP+, and octyl-TPP+ similarly to quinone-containing analog (SkQ1) inhibited growth of the Gram-positive bacterium Bacillus subtilis, wherein the inhibitory effect was upregulated with growing lipophilicity. These cations did not display toxic effect on growth of the Gram-negative bacterium Escherichia coli. It is assumed that the difference in toxic action on various bacterial species might be related to different permeability of bacterial coats for the examined triphenylphosphonium cations.

Keywords

permeating cation SkQ1 mitochondria uncoupling bacteria cytotoxicity 

Abbreviations

CF

5(6)-carboxyfluorescein

Cn-TPP+

alkyl-triphenylphosphonium cation

DiS-C3-(5)

potential-dependent carbocyanine probe

ΔμH+

mitochondrial transmembrane proton electrochemical gradient

ΔpH

pH gradient across the inner membrane of mitochondria

Δψ

mitochondrial membrane potential

FCCP

arbonyl cyanide p-trifluoromethoxyphenylhydrazone

Phe4P+

tetraphenylphosphonium cation

SkQ1

10-(plastoquinonyl)decyltriphenylphosphonium

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Copyright information

© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  • L. S. Khailova
    • 1
  • P. A. Nazarov
    • 1
  • N. V. Sumbatyan
    • 2
  • G. A. Korshunova
    • 1
  • T. I. Rokitskaya
    • 1
  • V. I. Dedukhova
    • 1
  • Yu. N. Antonenko
    • 1
  • V. P. Skulachev
    • 1
    • 3
  1. 1.Lomonosov Moscow State UniversityBelozersky Institute of Physico-Chemical BiologyMoscowRussia
  2. 2.Lomonosov Moscow State UniversityFaculty of ChemistryMoscowRussia
  3. 3.Lomonosov Moscow State UniversityInstitute of MitoengineeringMoscowRussia

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