Biochemistry (Moscow)

, Volume 79, Issue 10, pp 1081–1100 | Cite as

Prevention of peroxidation of cardiolipin liposomes by quinol-based antioxidants

  • A. V. Lokhmatikov
  • N. E. Voskoboynikova
  • D. A. Cherepanov
  • N. V. Sumbatyan
  • G. A. Korshunova
  • M. V. Skulachev
  • H. -J. Steinhoff
  • V. P. Skulachev
  • A. Y. Mulkidjanian
Review

Abstract

In mammalian mitochondria, cardiolipin molecules are the primary targets of oxidation by reactive oxygen species. The interaction of oxidized cardiolipin molecules with the constituents of the apoptotic cascade may lead to cell death. In the present study, we compared the effects of quinol-containing synthetic and natural amphiphilic antioxidants on cardiolipin peroxidation in a model system (liposomes of bovine cardiolipin). We found that both natural ubiquinol and synthetic antioxidants, even being introduced in micro- and submicromolar concentrations, fully protected the liposomal cardiolipin from peroxidation. The duration of their action, however, varied; it increased with the presence of either methoxy groups of ubiquinol or additional reduced redox groups (in the cases of rhodamine and berberine derivates). The concentration of ubiquinol in the mitochondrial membrane substantially exceeds the concentrations of antioxidants we used and would seem to fully prevent peroxidation of membrane cardiolipin. In fact, this does not happen: cardiolipin in mitochondria is oxidized, and this process can be blocked by amphiphilic cationic antioxidants (Y. N. Antonenko et al. (2008) Biochemistry (Moscow), 73, 1273–1287). We suppose that a fraction of mitochondrial cardiolipin could not be protected by natural ubiquinol; in vivo, peroxidation most likely threatens those cardiolipin molecules that, being bound within complexes of membrane proteins, are inaccessible to the bulky hydrophobic ubiquinol molecules diffusing in the lipid bilayer of the inner mitochondrial membrane. The ability to protect these occluded cardiolipin molecules from peroxidation may explain the beneficial therapeutic action of cationic antioxidants, which accumulate electrophoretically within mitochondria under the action of membrane potential.

Key words

apoptosis respiratory supercomplexes reactive oxygen species penetrating cations plastoquinol SkQ1 

Abbreviations

AAPH

2,2′-azobis(2-aminopropane)dihydrochloride

BHT

2,6-di-tert-butyl-4-methylphenol

CL

cardiolipin

C11-BODIPY 581/591

4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid

decPQH2

decylplastoquinol

decUQH2

decylubiquinol

HPMC

6-hydroxy-2,2,5,7,8-pentamethylbenzochroman

MeO-AMVN

2,2′-azo-bis(4-methoxy-2,4-dimethylvaleronitryl)

MitoQH2

10-(2,3-dimethoxy-5-methyl-1,4-benzoquinonyl-6)decyltriphenylphosphonium

ML

methyl linoleate

POPC

1-palmitoyl-2-oleoylphosphatidylcholine

POPG

1-palmitoyl-2-oleoylphosphatidylglycerol

Q6H2

ubiquinol-6

Q10H2

ubiquinol-10

ROS

reactive oxygen species

SkQ

compounds composed of penetrating cation and quinone

SkQH2

reduced (quinol) forms of SkQ

SkQ1H2

10-(plastoquinonyl-6)decyltriphenylphosphonium

SkQ3H2

10-(methylplastoquinonyl-6)decyltriphenylphosphonium

SkQBerbH2

13-[9-(6-plastoquinonyl)nonyloxycarbonylmethyl]dihydroberberine

SkQT1H2

10-(p-toluquinonyl)decyltriphenylphosphonium

SkQR1H2

10-(plastoquinonyl-6)decyldihydrorhodamine 19

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Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  • A. V. Lokhmatikov
    • 1
    • 2
  • N. E. Voskoboynikova
    • 1
  • D. A. Cherepanov
    • 3
  • N. V. Sumbatyan
    • 4
  • G. A. Korshunova
    • 5
  • M. V. Skulachev
    • 6
  • H. -J. Steinhoff
    • 1
  • V. P. Skulachev
    • 2
    • 5
  • A. Y. Mulkidjanian
    • 1
    • 2
    • 5
  1. 1.School of PhysicsUniversity of OsnabruckOsnabruckGermany
  2. 2.School of Bioengineering and BioinformaticsLomonosov Moscow State UniversityMoscowRussia
  3. 3.Frumkin Institute of Physical Chemistry and ElectrochemistryRussian Academy of SciencesMoscowRussia
  4. 4.School of ChemistryLomonosov Moscow State UniversityMoscowRussia
  5. 5.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  6. 6.Institute of MitoengineeringLomonosov Moscow State UniversityMoscowRussia

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