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Superoxide activates mitochondrial uncoupling proteins.
Nature. 2002 Jan 03; 415(6867):96-9.Nat

Abstract

Uncoupling protein 1 (UCP1) diverts energy from ATP synthesis to thermogenesis in the mitochondria of brown adipose tissue by catalysing a regulated leak of protons across the inner membrane. The functions of its homologues, UCP2 and UCP3, in other tissues are debated. UCP2 and UCP3 are present at much lower abundance than UCP1, and the uncoupling with which they are associated is not significantly thermogenic. Mild uncoupling would, however, decrease the mitochondrial production of reactive oxygen species, which are important mediators of oxidative damage. Here we show that superoxide increases mitochondrial proton conductance through effects on UCP1, UCP2 and UCP3. Superoxide-induced uncoupling requires fatty acids and is inhibited by purine nucleotides. It correlates with the tissue expression of UCPs, appears in mitochondria from yeast expressing UCP1, and is absent in skeletal muscle mitochondria from UCP3 knockout mice. Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria.

Authors+Show Affiliations

Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11780125

Citation

Echtay, Karim S., et al. "Superoxide Activates Mitochondrial Uncoupling Proteins." Nature, vol. 415, no. 6867, 2002, pp. 96-9.
Echtay KS, Roussel D, St-Pierre J, et al. Superoxide activates mitochondrial uncoupling proteins. Nature. 2002;415(6867):96-9.
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., Clapham, J. C., & Brand, M. D. (2002). Superoxide activates mitochondrial uncoupling proteins. Nature, 415(6867), 96-9.
Echtay KS, et al. Superoxide Activates Mitochondrial Uncoupling Proteins. Nature. 2002 Jan 3;415(6867):96-9. PubMed PMID: 11780125.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Superoxide activates mitochondrial uncoupling proteins. AU - Echtay,Karim S, AU - Roussel,Damien, AU - St-Pierre,Julie, AU - Jekabsons,Mika B, AU - Cadenas,Susana, AU - Stuart,Jeff A, AU - Harper,James A, AU - Roebuck,Stephen J, AU - Morrison,Alastair, AU - Pickering,Susan, AU - Clapham,John C, AU - Brand,Martin D, PY - 2002/1/10/pubmed PY - 2002/1/30/medline PY - 2002/1/10/entrez SP - 96 EP - 9 JF - Nature JO - Nature VL - 415 IS - 6867 N2 - Uncoupling protein 1 (UCP1) diverts energy from ATP synthesis to thermogenesis in the mitochondria of brown adipose tissue by catalysing a regulated leak of protons across the inner membrane. The functions of its homologues, UCP2 and UCP3, in other tissues are debated. UCP2 and UCP3 are present at much lower abundance than UCP1, and the uncoupling with which they are associated is not significantly thermogenic. Mild uncoupling would, however, decrease the mitochondrial production of reactive oxygen species, which are important mediators of oxidative damage. Here we show that superoxide increases mitochondrial proton conductance through effects on UCP1, UCP2 and UCP3. Superoxide-induced uncoupling requires fatty acids and is inhibited by purine nucleotides. It correlates with the tissue expression of UCPs, appears in mitochondria from yeast expressing UCP1, and is absent in skeletal muscle mitochondria from UCP3 knockout mice. Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria. SN - 0028-0836 UR - https://www.unboundmedicine.com/medline/citation/11780125/Superoxide_activates_mitochondrial_uncoupling_proteins_ L2 - https://doi.org/10.1038/415096a DB - PRIME DP - Unbound Medicine ER -