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

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

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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/10.1007/s11827-008-1006-7

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Keywords

  • Rotenone
  • Mitochondrial Respiration
  • Supplement Series
  • Liver Mitochondrion
  • Dicumarol