The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
The Mechanism of Superoxide Production by the Antimycin-inhibited Mitochondrial Q-cycle
Open accessAbstract
Superoxide production from antimycin-inhibited complex III in isolated mitochondria first increased to a maximum then decreased as substrate supply was modulated in three different ways. In each case, superoxide production had a similar bell-shaped relationship to the reduction state of cytochrome b(566), suggesting that superoxide production peaks at intermediate Q-reduction state because it comes from a semiquinone in the outer quinone-binding site in complex III (Q(o)). Imposition of a membrane potential changed the relationships between superoxide production and b(566) reduction and between b(562) and b(566) redox states, suggesting that b(562) reduction also affects semiquinone concentration and superoxide production. To assess whether this behavior was consistent with the Q-cycle mechanism of complex III, we generated a kinetic model of the antimycin-inhibited Q(o) site. Using published rate constants (determined without antimycin), with unknown rate constants allowed to vary, the model failed to fit the data. However, when we allowed the rate constant for quinol oxidation to decrease 1000-fold and the rate constant for semiquinone oxidation by b(566) to depend on the b(562) redox state, the model fit the energized and de-energized data well. In such fits, quinol oxidation was much slower than literature values and slowed further when b(566) was reduced, and reduction of b(562) stabilized the semiquinone when b(566) was oxidized. Thus, superoxide production at Q(o) depends on the reduction states of b(566) and b(562) and fits the Q-cycle only if particular rate constants are altered when b oxidation is prevented by antimycin. These mechanisms limit superoxide production and short circuiting of the Q-cycle when electron transfer slows.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“This ROS-promoting effect of complex II inhibitors can be related to a partially oxidized Q-pool that maximizes ROS production by complex III upon antimycin inhibition [25,32,33].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [33]
In the citing paper
“Under very specific conditions, complex II can also modulate the superoxide production at the Q o site of complex III [15,16,33] (Fig. 3B).”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [33]
In the citing paper
“This can be explained by an increased oxidation of the Q-pool, since it was shown that the superoxide generation at the Q o site is maximal at intermediate reduction states of the ubiquinone pool if the Q i site is blocked by antimycin A [25,32,33].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [33]
In the citing paper
“In isolated rat heart mitochondria, complex II inhibitors can increase the superoxide production at the Q o site of complex III only under the specific conditions indicated in Section 3.2 and Fig. 3B [15,16,33], i.e. when succinate is the predominant substrate and under conditions of 'oxidant-induced reduction'.”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [33]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207
The Free Radical Theory of Aging Matures
BECKMAN, K. B., & AMES, B. N. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.2.547 · Cited by 3,879
Boveris, A., & Chance, B. (1973) · Biochemical Journal · doi:10.1042/bj1340707 · Cited by 2,626
Topology of superoxide production from different sites in the mitochondrial electron transport chain
St-Pierre, J., Buckingham, J. A., Roebuck, S. J., & Brand, M. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207217200 · Cited by 1,545
Self-citationThe sites and topology of mitochondrial superoxide production
Brand, M. D. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.01.003 · Cited by 1,217
Self-citationComplex iii releases superoxide to both sides of the inner mitochondrial membrane
Muller, F. L., Liu, Y., & Van Remmen, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407715200 · Cited by 1,036
Superoxide production by the mitochondrial respiratory chain
Turrens, J. F. (1997) · Bioscience Reports · doi:10.1023/a:1027374931887 · Cited by 903
Barja, G. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.07.005 · Cited by 653
The protonmotive Q cycle: A general formulation
Mitchell, P. D. (1975) · FEBS Letters · doi:10.1016/0014-5793(75)80359-0 · Cited by 626
Structure and Function of CytochromebcComplexes
Berry, E. A., Guergova-Kuras, M., Huang, L.-S., & Crofts, A. R. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.1005 · Cited by 501
Lambert, A. J., & Brand, M. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406576200 · Cited by 480
Self-citationThe Cytochrome bc1 Complex: Function in the Context of Structure
Crofts, A. R. (2004) · Annual Review of Physiology · doi:10.1146/annurev.physiol.66.032102.150251 · Cited by 474
Generation of Reactive Oxygen Species in the Reaction Catalyzed by α-Ketoglutarate Dehydrogenase
Tretter, L., & Ádám‐Vizi, V. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1842-04.2004 · Cited by 455
Boveris, A., & Cadenas, E. (1975) · FEBS Letters · doi:10.1016/0014-5793(75)80928-8 · Cited by 401
Crofts, A. R., Meinhardt, S. W., Jones, K. R., & Snozzi, M. (1983) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(83)90120-2 · Cited by 394
The mechanism of mitochondrial superoxide production by the cytochrome bc1 complex
Dröse, S., & Brandt, U. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803236200 · Cited by 386
Biochemical and Osmotic Properties of Skeletal Muscle Mitochondria
Chappell, J., & PERRY, S. V. (1954) · Nature · doi:10.1038/1731094a0 · Cited by 291
Rolfe, D. F. S., Hulbert, A. J., & Brand, M. D. (1994) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(94)90062-0 · Cited by 243
Self-citationOxidative damage to mitochondria and aging
Remmen, H. V. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00093-6 · Cited by 233
Bioenergetics: a practical approach
(1997) · General Pharmacology The Vascular System · doi:10.1016/s0306-3623(97)84211-5 · Cited by 212
On the Redox Potentials of Ubiquinone and Cytochrome b in the Respiratory Chain
Urban, P. F., & Klingenberg, M. (1969) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1969.tb00640.x · Cited by 189
Hoffman, D. L., & Brookes, P. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809512200 · Cited by 184
Cape, J. L., Bowman, M. K., & Kramer, D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702621104 · Cited by 172
Brasseur, G., Sarıbaş, A. S., & Daldal, F. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00051-5 · Cited by 171
Multiple Q-Cycle Bypass Reactions at the Qo Site of the Cytochrome bc1 Complex
Muller, F., Crofts, A. R., & Kramer, D. M. (2002) · Biochemistry · doi:10.1021/bi025581e · Cited by 163
How rapid are the internal reactions of the ubiquinol:cytochrome c 2 oxidoreductase?
Crofts, A. R., & Wang, Z. (1989) · Photosynthesis Research · doi:10.1007/bf00114768 · Cited by 160
Link, T. A. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00772-2 · Cited by 149
Steered Molecular Dynamics Simulation of the Rieske Subunit Motion in the Cytochrome bc1 Complex
Izrailev, S., Crofts, A. R., Berry, E. A., & Schulten, K. J. (1999) · Biophysical Journal · doi:10.1016/s0006-3495(99)77022-0 · Cited by 139
de Vries, S., Albracht, S. P. J., BERDEN, J. A., & Slater, E. C. (1982) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(82)90276-6 · Cited by 132
On the Mechanism of Quinol Oxidation in thebc1 Complex
Jünemann, S., Heathcote, P., & Rich, P. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.34.21603 · Cited by 108
Rottenberg, H., Covián, R., & Trumpower, B. L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.017376 · Cited by 106
Crofts, A. R., Guergova-Kuras, M., Huang, L.-S., Kuras, R., Zhang, Z., & Berry, E. A. (1999) · Biochemistry · doi:10.1021/bi990961u · Cited by 98
The role of cytochrome b-566 in the electron-transfer chain of Rhodopseudomonas sphaeroides
Meinhardt, S. W., & Crofts, A. R. (1983) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(83)90121-4 · Cited by 94
de Vries, S., Albracht, S. P. J., BERDEN, J. A., Marres, C. A. M., & Slater, E. C. (1983) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(83)90013-0 · Cited by 93
Mulkidjanian, A. Y. (2005) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2005.03.009 · Cited by 93
van den Berg, W. H., Prince, R. C., Bashford, C. L., Takamiya, K., Bonner, W. D., & Dutton, P. L. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)86934-x · Cited by 92
Harman, D. (1998) · PubMed · Cited by 90
Treberg, J. R., Quinlan, C. L., & Brand, M. D. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07693.x · Cited by 86
Self-citationRole of mobility of redox components in the inner mitochondrial membrane
Lenaz, G. (1988) · The Journal of Membrane Biology · doi:10.1007/bf01872322 · Cited by 84
Trumpower, B. L. (1976) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(76)91110-4 · Cited by 80
Forquer, I., Covián, R., Bowman, M. K., Trumpower, B. L., & Kramer, D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605119200 · Cited by 77
Crofts, A. R., Shinkarev, V. P., Kolling, D. R. J., & Hong, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305461200 · Cited by 71
Cooley, J. W., Ohnishi, T., & Daldal, F. (2005) · Biochemistry · doi:10.1021/bi050571+ · Cited by 67
Sarewicz, M., Borek, A., Cieluch, E., Świerczek, M., & Osyczka, A. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.07.005 · Cited by 63
Integration of CellDesigner and SABIO-RK.
Funahashi, A., Jouraku, A., Matsuoka, Y., & Kitano, H. (2007) · PubMed · Cited by 62
Across Membrane Communication between the Qo and Qi Active Sites of Cytochrome bc1
Cooley, J. W., Lee, D., & Daldal, F. (2009) · Biochemistry · doi:10.1021/bi802216h · Cited by 54
Fato, R., Cavazzoni, M., Castelluccio, C., Castelli, G. P., Palmer, G., Esposti, M. D., & Lenaz, G. (1993) · Biochemical Journal · doi:10.1042/bj2900225 · Cited by 50
Erecińska, M., & Wilson, D. F. (1976) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(76)90333-7 · Cited by 41
Esposti, M. D., & Lenaz, G. (1982) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(82)90098-6 · Cited by 39
West, I. C., Mitchell, P. D., & Rich, P. R. (1988) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(88)90053-9 · Cited by 24
The kinetic mechanism of ubiquinol: Cytochrome c reductase at steady state
Esposti, M. D., & Lenaz, G. (1991) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(91)90415-f · Cited by 23
Effect of ubiquinone extraction on the reaction of the mitochondrialbc 1 complex with ferricyanide
Pasquali, P., Esposti, M. D., Landi, L., Cabrini, L., & Lenaz, G. (1985) · Journal of Bioenergetics and Biomembranes · doi:10.1007/bf00751105 · Cited by 4
Research works printed but not linked: 2
- Harman, 1998, J. Int. Fed. Clin. Chem., 10, 24
- Funahashi, 2007, In Silico Biol., 7, S81
Cited by
Sorted by citations
Mitochondrial electron transport chain, ROS generation and uncoupling (Review)
Zhao, R., Jiang, S., Zhang, L., & Yu, Z. (2019) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2019.4188 · Cited by 1,497
Brand, M. D. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.001 · Cited by 1,063
Self-citationQuinlan, C. L., Orr, A. L., Perevoshchikova, I. V., Treberg, J. R., Ackrell, B. A., & Brand, M. D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.374629 · Cited by 670
Self-citationSites of reactive oxygen species generation by mitochondria oxidizing different substrates
Quinlan, C. L., Perevoshchikova, I. V., Hey‐Mogensen, M., Orr, A. L., & Brand, M. D. (2013) · Redox Biology · doi:10.1016/j.redox.2013.04.005 · Cited by 608
Self-citationSuccinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis
Tretter, L., Patócs, A., & Chinopoulos, C. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.03.012 · Cited by 550
Metadata
- Authors
- Quinlan, C. L., Gerencser, A. A., Treberg, J. R., & Brand, M. D.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Quinlan, Casey L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 286
- Issue
- 36
- Pages
- 31361-31372
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3173136
- OpenAlex
- W2009383015
- Cited by
- 200
- References
- 52
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 11 · 2023: 19 · 2022: 11 · 2021: 21 · 2020: 17 · 2019: 9 · 2018: 11 · 2017: 11 · 2016: 13 · 2015: 10 · 2014: 17 · 2013: 14 · 2012: 9
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG033542, PL1AG032118, P01AG025901)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- superoxide production, antimycin, mitochondrial complex III, Q-cycle, cytochrome b562, semiquinone, kinetic modeling, electron transfer, membrane potential, mitochondrial respiration, reactive oxygen species
- MeSH terms
- Animals, Anti-Bacterial Agents, Antimycin A, Cytochrome b Group, Electron Transport, Female, Kinetics, Mitochondria, Oxidation-Reduction, Quinones, Superoxides, Electron Transport Complex III, Rats, Wistar, Escherichia coli Proteins, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
