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Interaction of positively charged ubiquinone analog (MitoQ10) with DT-diaphorase from liver mitochondria

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Effects of the coenzyme Q analog (MitoQ10) carrying a positively charged decyltetraphenylphosphonium group on functional activity of phosphorylating liver mitochondria were studied. Using inhibitory analysis it was found that at micromolar concentrations this quinone is reduced by NADH-dependent DT-diaphorase. Under conditions of malate oxidation, MitoQ10 stimulates electron transfer from NADH to oxygen by shunting the block of rotenone-induced electron transport in Complex I. Steady-state mitochondrial respiration induced by rotenone and MitoQ10 (1 μM), as well as K3 shunt are both blocked by the DT-diaphorase inhibitor dicumarol, the Complex III inhibitor myxothiazole, and the cytochrome oxidase inhibitor cyanide. The electron transport chain induced in liver mitochondria by MitoQ10 in the presence of rotenone appears as follows: NADH → DT-diaphorase → MitoQ10 → Complex III → Complex IV → O2. Under conditions of malate (but not succinate) oxidation, MitoQ10 and high concentrations of vitamin K3 induce in mitochondria cyanide-resistant respiration and opening of the nonspecific pore eventually resulting in inhibition of oxidative phosphorylation. It is concluded that MitoQ10 should be regarded as an analog of hydrophilic quinones (vitamin K3, duroquinone, etc.) widely known as substrates for mitochondrial DT-diaphorase not interacting with CoQ10 rather than as a natural CoQ10 analog.

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Abbreviations

MitoQ:

mitoquinone

C12TPP:

triphenyldodecylphosphonium

BSA:

bovine serum albumin

FCCP:

trifluoromethylphenylhydrazonecarbonylcyanide

EGTA:

(ethylenedioxy)diethylenedinitryltetraacetic acid

EDTA:

ethylenediaminetetraacetic acid

ROS:

reactive oxygen species

References

  1. Turunena, M., Olssonc, J., and Dallner, G., Metabolism and Function of Coenzyme Q, Biochim. et Biophys. Acta, 2004, vol. 1660, pp. 171–199.

    Article  Google Scholar 

  2. Sies, H. and Packer, L., Quinones and Quinone Enzymes, Academic Press, 2004.

    Google Scholar 

  3. Asin-Cayuela, J., Manas, A.R., James, A.M., Smith, R.A., and Murphy, M.P., Fine-Tuning the Hydrophobicity of a Mitochondria-Targeted Antioxidant, FEES Lett., 2004, vol. 571, pp. 9–16.

    Article  CAS  Google Scholar 

  4. Murphy, M.P. and Smith, R., Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations, Annu. Rev. Pharmacol. Toxicol., 2007, vol. 47, pp. 629–656.

    Article  CAS  Google Scholar 

  5. James, A.M., Cocheme, H.M., Smith, R.A., and Murphy, M.P., Interactions of Mitochondria-Targeted and Untargeted Ubiquinones with the Mitochondrial Respiratory Chain and Reactive Oxygen Species. Implications for the Use of Exogenous Ubiquinones As Therapies and Experimental Tools, J. Biol. Chem., 2005, vol. 280, pp. 21295–21312.

    Article  CAS  Google Scholar 

  6. Koopman, W.J., Verkaart, S., Visch, H.J., van Der Westhuizen, F.H., Murphy, M.P., van Den Heuvel, L.W., Smeitink, J.A., and Willems, P.H., Inhibition of Complex I of the Electron Transport Chain Causes O--Mediated Mitochondrial Outgrowth, Am. J. Physiol. Cell Physiol., 2005, vol. 288, pp. 1440–1450.

    Article  Google Scholar 

  7. Covian, R. and Trumpower, B.L., Regulatory Interactions between Ubiquinol Oxidation and Ubiquinone Reduction Sites in the Dimeric Cytochrome be 1 Complex, J. Biol. Chem., 2006, vol. 281, pp. 30925–30932.

    Article  CAS  Google Scholar 

  8. Johnson, D. and Lardy, H., Isolation of Liver or Kidney Mitochondria, Meth. Enzymol., 1967, vol. 10, pp. 94–96.

    Article  CAS  Google Scholar 

  9. Schwartz, J.E. and Durham, B.C., Evaluation of Three Methods of Protein Analysis for Serum and Heart Homogenates, Ann. Clin. Lab. Sci., 1979, vol. 9(2), pp. 139–143.

    CAS  PubMed  Google Scholar 

  10. Kelso, G.F., Porteous, C.M., Coulter, C.V., Hughes, G., Porteous, W.K., Ledgerwood, E.C., Smith, R.A., and Murphy, M.P., Selective Targeting of a Redox-Active Ubiquinone to Mitochondria Within Cells, J. Biol. Chem., 2001, vol. 276(7), pp. 4588–4596.

    Article  CAS  Google Scholar 

  11. Kolesova, G.M., Vishnivetsky S.A., and Yaguzhinsky, L.S., Study of Mechanism of Cyanide-Resistant Respiration of Liver Mitochondria in the Presence of Menadione, Biokhimiya (Rus.), 1989, vol. 54, pp. 103–111.

    CAS  Google Scholar 

  12. Kolesova, G.M., Karnaukhova, L.V., Segal', N.K., and Yaguzhinsky, L. S., The Effect of Inhibitors of the Q-Cycle on Cyano-Resistant Oxidation of Malate by Rat Liver Mitochondria in the Presence of Menadione, Biokhimiya (Rus.), 1993, vol. 58, pp. 1630–1640.

    CAS  Google Scholar 

  13. Chance, B. and Hollunger, G., The Interaction of Energy and Electron Transfer Reactions in Mitochondria. III. Substrate Requirements for Pyridine Nucleotide Reduction in Mitochondria, J. Biol. Chem., 1961, vol. 236(5), pp. 1555–1561.

    Article  CAS  Google Scholar 

  14. McStay, G.P., Clarke, S.J., and Halestrap, A.P., Role of Critical Thiol Groups on the Matrix Surface of the Adenine Nucleotide Translocase in the Mechanism of the Mitochondrial Permeability Transition Pore, Biochem. J., 2002, vol. 367, pp. 541–548.

    Article  CAS  Google Scholar 

  15. Doughan, A.K. and Dikalov, S.I., Mitochondrial Redox Cycling of Mitoquinone Leads to Superoxide Production and Cellular Apoptosis, Antioxidants & Redox Signaling, 2007, vol. 9, pp. 1825–1836.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    V. I. Kargin, K. A. Motovilov, M. Yu. Vyssokikh & L. S. Yaguzhinsky

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  1. V. I. Kargin
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  2. K. A. Motovilov
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  3. M. Yu. Vyssokikh
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  4. L. S. Yaguzhinsky
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Correspondence to L. S. Yaguzhinsky.

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Original Russian Text © V.I. Kargin, K.A. Motovilov, M.Yu. Vyssokikh, L.S. Yaguzhinsky, 2008, published in Biologicheskie Membrany, 2008, Vol. 25, No. 1, pp. 34–40.

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Kargin, V.I., Motovilov, K.A., Vyssokikh, M.Y. et al. Interaction of positively charged ubiquinone analog (MitoQ10) with DT-diaphorase from liver mitochondria. Biochem. Moscow Suppl. Ser. A 2, 33–39 (2008). https://doi.org/10.1134/S1990747808010066

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  • DOI: https://doi.org/10.1134/S1990747808010066

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