The site of inhibition of mitochondrial electron transfer by coenzyme Q analogues

Roberts, Henry; Choo, Wan Mee; Smith, Stuart; Marzuki, Sangkot; Linnane, Anthony W.; Porter, Thomas H.; Folkers, Karl

doi:10.1016/0003-9861(78)90093-0

Cited by 76 publications

(7 citation statements)

References 25 publications

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“…HUNQ does not inhibit succinate dehydrogenase activity at the HUNQ concentrations at which total inhibition of succinate oxidase occurs. Since cytochrome oxidase activity is also unaffected, the inhibition reported here occurs only in the b-cl region as suggested by Roberts et al (1978).…”

Section: Discussionsupporting

confidence: 64%

Effects of 2-hydroxy-3-undecyl-1,4-naphthoquinone on respiration of electron transport particles and mitochondria: topographical location of the Rieske iron-sulfur protein and the quinone binding site

Harmon¹,

Struble²

1983

Biochemistry

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2-Hydroxy-3-undecyl-1,4-naphthoquinone is a quinone analogue that inhibits mitochondrial respiration in the cytochrome b-c1 region with an apparent Ki of 2.5 X 10(-7) M. In electron transport particles, it prevents the reduction of cytochrome c1 by succinate but not its oxidation by oxygen and prevents oxidation of cytochrome b but not its reduction by succinate. The analogue increases the amount of steady-state cytochrome b reduction in actively respiring particles. It inhibits oxidant-induced reduction of cytochrome b in the presence of antimycin. Inhibition of succinate oxidase activity in electron transport particles is independent of the pH of the suspending medium while at pH values above 8 with mitochondria, inhibition decreases. Since the apparent pK of the bound quinone is pH 6.6, the pH dependency of the inhibition is likely due to the pK of the Rieske iron-sulfur center (pH 8). The Rieske center and thus the quinone binding site are located on the cytoplasmic face of the inner membrane.

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Section: Discussionsupporting

confidence: 64%

Effects of 2-hydroxy-3-undecyl-1,4-naphthoquinone on respiration of electron transport particles and mitochondria: topographical location of the Rieske iron-sulfur protein and the quinone binding site

Harmon¹,

Struble²

1983

Biochemistry

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“…[5][6][7][8] A subgroup of quinones are the naphthoquinones that have various biological properties. [9][10][11][12][13][14][15][16] Natural and synthetic 1,4-naphthoquinone derivatives have been recognized for their biological activities, and thus, enormous interest has been stimulated in this class of com-pounds. [17][18][19][20][21][22][23] There have also been reports on naphthoquinone sulfides demonstrating anticancer and antifungal activities.…”

Section: Introductionmentioning

confidence: 99%

Laccase‐Catalyzed CS and CC Coupling for a One‐Pot Synthesis of 1,4‐Naphthoquinone Sulfides and 1,4‐Naphthoquinone Sulfide Dimers

et al. 2013

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Oxidative CS and CC bond formation with aryl and alkyl thiols was catalyzed under mild conditions in a reaction vessel open to air at pH 4.5 in the presence of a commercial laccase (Novozym 51003 or Suberase) and a cosolvent (DMF) to afford 1,4‐naphthoquinone sulfides. Although both monothiolation and dithiolation of the 1,4‐naphthohydroquinone were accomplished, the latter was favored. In addition, unprecedented dimerization of monothiolated intermediates occurred through CC coupling. These commercial laccases provide a facile and a more environmentally friendly synthetic approach to both 1,4‐naphthoquinone sulfides and 1,4‐naphthoquinone sulfide dimers.

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“…Yu et al, 1977, 1981. Furthermore, various inhibitors of electron flow in Complex III are ubiquinone analogues (Roberts et al, 1978;Trumpower & Haggerty, 1980) and may act at more than one site (Convent etal., 1978;Izzo et al, 1978).…”

mentioning

confidence: 99%

The pathway of electron flow through ubiquinol:cytochrome c oxidoreductase in the respiratory chain. Evidence from inhibition studies for a modified ‘Q cycle’

Halestrap¹

1982

Biochemical Journal

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1. Cytochrome spectra of the liver and heart mitochondria incubated under various conditions are presented to compare the effects of antimycin, colletotrichin and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) additions. 2. Under aerobic conditions, in State 4, in the presence of uncoupler or in the presence of cyanide, all three inhibitors caused oxidation of cytochromes c and c1, but different changes in the spectra of the b cytochromes. Antimycin caused oxidation of a peak at 558 nm and reduction of peaks at 562 nm and 566 nm, whereas colletotrichin caused reduction of peaks at 558 nm and 566 nm and oxidation at 562 nm. HQNO had an effect on the spectra intermediate between those of the two other inhibitors. 3. Under aerobic conditions in the presence of 5 mM-succinate and 5 mM-fumarate, antimycin caused reduction of a peak at 566 nm and oxidation of a peak at 558 nm, whereas colletotrichin had the reverse effect and HQNO caused reduction of a peak at 562 nm. 4. Colletotrichin inhibition of the ADP-stimulated oxidation of glutamate + malate was enhanced by succinate addition and declined again with rotenone addition. Similar but smaller effects were seen with inhibition by antimycin and HQNO. 5. Cytochrome spectra are shown of the effects of ADP and uncoupler addition to stimulate respiration progressively. 6. The results are interpreted in terms of a modified 'Q cycle' [Mitchell (1976) J. Theor. Biol. 62, 327-367] in which the three inhibitors are postulated to displace ubiquinone and ubisemiquinone specifically bound to cytochromes b on both sides of the membrane. 7. It is suggested that cytochromes b558 and b566 are the same b cytochrome located on the outer surface of the membrane, but binding ubisemiquinone or colletotrichin and ubiquinone or antimycin respectively. Cytochrome b562 is postulated to be on the inner surface of the mitochondrial membrane and to bind either ubiquinone or ubisemiquinone, HQNO would bind to the reduced form of the cytochrome and colletotrichin to the oxidized form. 8. Sites for the locus of action of glucagon and the protonmotive force on electron flow are suggested.

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The site of inhibition of mitochondrial electron transfer by coenzyme Q analogues

Cited by 76 publications

References 25 publications

Effects of 2-hydroxy-3-undecyl-1,4-naphthoquinone on respiration of electron transport particles and mitochondria: topographical location of the Rieske iron-sulfur protein and the quinone binding site

Effects of 2-hydroxy-3-undecyl-1,4-naphthoquinone on respiration of electron transport particles and mitochondria: topographical location of the Rieske iron-sulfur protein and the quinone binding site

Laccase‐Catalyzed CS and CC Coupling for a One‐Pot Synthesis of 1,4‐Naphthoquinone Sulfides and 1,4‐Naphthoquinone Sulfide Dimers

The pathway of electron flow through ubiquinol:cytochrome c oxidoreductase in the respiratory chain. Evidence from inhibition studies for a modified ‘Q cycle’

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