Production of endogenous matrix superoxide from mitochondrial complex I leads to activation of uncoupling protein 3
Abstract
Superoxide generated using exogenous xanthine oxidase indirectly activates an uncoupling protein (UCP)‐mediated proton conductance of the mitochondrial inner membrane. We investigated whether endogenous mitochondrial superoxide production could also activate proton conductance. When respiring on succinate, rat skeletal muscle mitochondria produced large amounts of matrix superoxide. Addition of GDP to inhibit UCP3 markedly inhibited proton conductance and increased superoxide production. Both superoxide production and the GDP‐sensitive proton conductance were suppressed by rotenone plus an antioxidant. Thus, endogenous superoxide can activate the proton conductance of UCP3, which in turn limits mitochondrial superoxide production. These observations provide a departure point for studies under more physiological conditions.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Superoxide may act in feedback fashion to induce uncoupling and thereby control its own production.
“This has led to the idea that superoxide may act in feedback fashion to induce uncoupling and thereby control its own production (92, 306).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [306]
Cites
DETERMINATION OF SERUM PROTEINS BY MEANS OF THE BIURET REACTION
Gornall, A. G., Bardawill, C. J., & David, M. M. (1949) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)57021-6 · Cited by 16,164 · see citing works
Korshunov, S. S., Skulachev, V. P., & Starkov, A. A. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01159-9 · Cited by 1,727 · see citing works
Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria
Turrens, J. F., & Boveris, A. (1980) · Biochemical Journal · doi:10.1042/bj1910421 · Cited by 1,601 · see citing works
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 · see citing works
Self-citationSuperoxide activates mitochondrial uncoupling proteins
Echtay, K. S., Roussel, D., St-Pierre, J., Jekabsons, M. B., Cadenas, S., Stuart, J. A., Harper, J. A., Roebuck, S. J., Morrison, A., Pickering, S., et al. (2002) · Nature · doi:10.1038/415096a · Cited by 1,382 · see citing works
Self-citationGeneration of reactive oxygen species by the mitochondrial electron transport chain
Liu, Y., Fiskum, G., & Schubert, D. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00744.x · Cited by 1,260 · see citing works
Arsenijevic, D., Onuma, H., Pecqueur, C., Raimbault, S., Manning, B. S., Miroux, B., Couplan, E., Alves‐Guerra, M., Goubern, M., Surwit, R. S., et al. (2000) · Nature Genetics · doi:10.1038/82565 · Cited by 1,079 · see citing works
A role for uncoupling protein‐2 as a regulator of mitochondrial hydrogen peroxide generation
Nègre‐Salvayre, A., Hirtz, C., Carrera, G., Cazenave, R., Troly, M., Salvayre, R., Pénicaud, L., & Casteilla, L. (1997) · The FASEB Journal · doi:10.1096/fasebj.11.10.9271366 · Cited by 757 · see citing works
Nicholls, D. G. (1974) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1974.tb03899.x · Cited by 720 · see citing works
Energy metabolism in uncoupling protein 3 gene knockout mice
Vidal-Puig, A. J., Grujic, D., Zhang, C.-Y., Hagen, T., Boss, O., Ido, Y., Szczepanik, A., Wade, J., Mootha, V., Cortright, R., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m910179199 · Cited by 677 · see citing works
Nedergaard, J., Golozoubova, V., Matthias, A., Asadi, A., Jacobsson, A., & Cannon, B. (2001) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(00)00247-4 · Cited by 615 · see citing works
Votyakova, T. V., & Reynolds, I. J. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00548.x · Cited by 601 · see citing works
A signalling role for 4‐hydroxy‐2‐nonenal in regulation of mitochondrial uncoupling
Echtay, K. S., Esteves, T. C., Pakay, J. L., Jekabsons, M. B., Lambert, A. J., Portero‐Otín, M., Pamplona, R., Vidal‐Puig, A. J., Wang, S., Roebuck, S. J., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg412 · Cited by 597 · see citing works
Self-citationDependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age
Hansford, R. G., Hogue, B. A., & Mildaziene, V. (1997) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1022420007908 · Cited by 447 · see citing works
Superoxide Activates Mitochondrial Uncoupling Protein 2 from the Matrix Side
Echtay, K. S., Murphy, M. P., Smith, R. A. J., Talbot, D. A., & Brand, M. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208262200 · Cited by 388 · see citing works
Self-citationMurphy, M. P., Echtay, K. S., Blaikie, F. H., Asin-Cayuela, J., Cochemé, H. M., Green, K., Buckingham, J. A., Taylor, E. R., Hurrell, F., Hughes, G., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308529200 · Cited by 304 · see citing works
Self-citationSuperoxide and hydrogen peroxide production by Drosophila mitochondria
Miwa, S., St‐Pierre, J., Partridge, L., & Brand, M. D. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00464-7 · Cited by 298 · see citing works
Self-citationThe proton leak across the mitochondrial inner membrane
Brand, M. D. (1990) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(90)90232-s · Cited by 261 · see citing works
Self-citationUCP2 and UCP3 rise in starved rat skeletal muscle but mitochondrial proton conductance is unchanged
Cadenas, S., Buckingham, J. A., Samec, S., Seydoux, J., Din, N., Dulloo, A. G., & Brand, M. D. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01540-9 · Cited by 227 · see citing works
Self-citationO2 solubility in aqueous media determined by a kinetic method
Reynafarje, B., Costa, L. E., & Lehninger, A. L. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90381-1 · Cited by 226 · see citing works
Generating, Partitioning, Targeting and Functioning of Superoxide in Mitochondria
Liu, S. (1997) · Bioscience Reports · doi:10.1023/a:1027328510931 · Cited by 217 · see citing works
Bioenergetics: a practical approach
(1997) · General Pharmacology The Vascular System · doi:10.1016/s0306-3623(97)84211-5 · Cited by 211 · see citing works
A History of the First Uncoupling Protein, UCP1
Nicholls, D. G., & Rial, E. (1999) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1005436121005 · Cited by 201 · see citing works
Cadenas, S., Echtay, K. S., Harper, J. A., Jekabsons, M. B., Buckingham, J. A., Grau, E., Abuin, A., Chapman, H., Clapham, J. C., & Brand, M. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109736200 · Cited by 199 · see citing works
Self-citationBRAND, M. D., PAMPLONA, R., PORTERO-OTÍN, M., REQUENA, J. R., ROEBUCK, S. J., BUCKINGHAM, J. A., CLAPHAM, J. C., & CADENAS, S. (2002) · Biochemical Journal · doi:10.1042/bj20021077 · Cited by 184 · see citing works
Self-citationMitochondrial superoxide and aging: uncoupling-protein activity and superoxide production
Brand, M. D., Buckingham, J. A., Esteves, T. C., Green, K., Lambert, A. J., Miwa, S., Murphy, M. P., Pakay, J. L., Talbot, D. A., & Echtay, K. S. (2004) · Biochemical Society Symposia · doi:10.1042/bss0710203 · Cited by 182 · see citing works
Self-citationKrauss, S., Zhang, C., & Lowell, B. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012410699 · Cited by 173 · see citing works
Measurement of mitochondrial protonmotive force
Brand, M. D. (1995) · doi:10.1093/oso/9780199634897.003.0003 · Cited by 96 · see citing works
Self-citationEffects of magnesium and nucleotides on the proton conductance of rat skeletal-muscle mitochondria
Cadenas, S., & Brand, M. D. (2000) · Biochemical Journal · doi:10.1042/bj3480209 · Cited by 50 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The 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 · see citing works
Self-citationMitochondria and reactive oxygen species
Kowaltowski, A. J., de Souza-Pinto, N. C., Castilho, R. F., & Vercesi, A. E. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.05.004 · Cited by 1,162 · see citing works
Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins
Brand, M. D., Affourtit, C., Esteves, T. C., Green, K., Lambert, A. J., Miwa, S., Pakay, J. L., & Parker, N. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.05.034 · Cited by 1,032 · see citing works
Self-citationPhysiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3
Brand, M. D., & Esteves, T. C. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.06.002 · Cited by 785 · see citing works
Self-citationSivitz, W. I., & Yorek, M. A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2531 · Cited by 742 · see citing works
LAMBERT, A. J., & BRAND, M. D. (2004) · Biochemical Journal · doi:10.1042/bj20040485 · Cited by 470 · see citing works
Self-citationMitochondrial dysfunction in cardiovascular disease
Ballinger, S. W. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.02.014 · Cited by 405 · see citing works
The physiological regulation of uncoupling proteins
Nicholls, D. G. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.02.005 · Cited by 183 · see citing works
Disruption of mitochondrial redox circuitry in oxidative stress
Jones, D. P. (2006) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2006.07.008 · Cited by 176 · see citing works
Mitochondrial uncoupling and lifespan
Mookerjee, S. A., Divakaruni, A. S., Jastroch, M., & Brand, M. D. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.03.010 · Cited by 169 · see citing works
Self-citationA Possible Site of Superoxide Generation in the Complex I Segment of Rat Heart Mitochondria
Ohnishi, S. T., Ohnishi, T., Muranaka, S., Fujita, H., Kimura, H., Uemura, K., Yoshida, K.-I., & Utsumi, K. (2005) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-005-4117-y · Cited by 123 · see citing works
Reactive Oxygen and Targeted Antioxidant Administration in Endothelial Cell Mitochondria
O'Malley, Y., Fink, B. D., Ross, N. C., Prisinzano, T. E., & Sivitz, W. I. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608268200 · Cited by 123 · see citing works
Seifert, E. L., Bézaire, V., Estey, C., & Harper, M.-E. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803871200 · Cited by 104 · see citing works
Respiratory uncoupling by UCP1 and UCP2 and superoxide generation in endothelial cell mitochondria
Fink, B. D., Reszka, K. J., Herlein, J. A., Mathahs, M. M., & Sivitz, W. I. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00332.2004 · Cited by 53 · see citing works
- Authors
- Talbot, D. A., Lambert, A. J., & Brand, M. D.
- Affiliations
- MRC Mitochondrial Biology Unit (GB)
- Corresponding author
- Brand, Martin D
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2003-12-04
- Volume
- 556
- Issue
- 1-3
- Pages
- 111-115
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2052622056
- Cited by
- 131
- References
- 29
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 1 · 2018: 6 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 2 · 2012: 7
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- mitochondrial superoxide, complex I, UCP3, proton conductance, skeletal muscle mitochondria, GDP inhibition, rotenone, antioxidants, succinate respiration, mitochondrial reactive oxygen species
- MeSH terms
- Uncoupling Protein 3, Animals, Carrier Proteins, Guanosine Diphosphate, Hydrogen Peroxide, Ion Channels, Kinetics, Male, Membrane Potentials, Mitochondria, Muscle, Oxygen Consumption, Protons, Rotenone, Superoxides, Vitamin E, Rats, Wistar, Succinic Acid, Mitochondrial Proteins, Electron Transport Complex I, 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