Document Detail


Superoxide activates mitochondrial uncoupling proteins.
MedLine Citation:
PMID:  11780125     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Karim S Echtay; Damien Roussel; Julie St-Pierre; Mika B Jekabsons; Susana Cadenas; Jeff A Stuart; James A Harper; Stephen J Roebuck; Alastair Morrison; Susan Pickering; John C Clapham; Martin D Brand
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature     Volume:  415     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-07     Completed Date:  2002-01-29     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  96-9     Citation Subset:  IM    
Affiliation:
Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue, Brown / cytology,  metabolism
Animals
Carrier Proteins / genetics,  metabolism*
Food Deprivation
Gene Deletion
Glyburide / pharmacology
Hot Temperature
Intracellular Membranes / metabolism
Ion Channels
Islets of Langerhans / cytology,  metabolism
Kidney / cytology,  metabolism
Liver / cytology,  metabolism
Membrane Potentials / drug effects
Membrane Proteins / genetics,  metabolism*
Membrane Transport Proteins*
Mice
Mice, Knockout
Mitochondria / drug effects*,  metabolism*
Mitochondrial Proteins*
Muscle, Skeletal / cytology,  metabolism
Myocardium / cytology,  metabolism
Proteins / metabolism
Protons
Rats
Reactive Oxygen Species / metabolism
Saccharomyces cerevisiae / cytology,  genetics
Spleen / cytology,  metabolism
Superoxides / pharmacology*
Uncoupling Agents / metabolism*,  pharmacology
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Ion Channels; 0/Membrane Proteins; 0/Membrane Transport Proteins; 0/Mitochondrial Proteins; 0/Proteins; 0/Protons; 0/Reactive Oxygen Species; 0/Uncoupling Agents; 0/mitochondrial uncoupling protein; 0/mitochondrial uncoupling protein 2; 0/mitochondrial uncoupling protein 3; 10238-21-8/Glyburide; 11062-77-4/Superoxides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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