Document Detail


The basal proton conductance of skeletal muscle mitochondria from transgenic mice overexpressing or lacking uncoupling protein-3.
MedLine Citation:
PMID:  11707458     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The ability of native uncoupling protein-3 (UCP3) to uncouple mitochondrial oxidative phosphorylation is controversial. We measured the expression level of UCP3 and the proton conductance of skeletal muscle mitochondria isolated from transgenic mice overexpressing human UCP3 (UCP3-tg) and from UCP3 knockout (UCP3-KO) mice. The concentration of UCP3 in UCP3-tg mitochondria was approximately 3 microg/mg protein, approximately 20-fold higher than the wild type value. UCP3-tg mitochondria had increased nonphosphorylating respiration rates, decreased respiratory control, and approximately 4-fold increased proton conductance compared with the wild type. However, this increased uncoupling in UCP3-tg mitochondria was not caused by native function of UCP3 because it was not proportional to the increase in UCP3 concentration and was neither activated by superoxide nor inhibited by GDP. UCP3 was undetectable in mitochondria from UCP3-KO mice. Nevertheless, UCP3-KO mitochondria had unchanged respiration rates, respiratory control ratios, and proton conductance compared with the wild type under a variety of assay conditions. We conclude that uncoupling in UCP3-tg mice is an artifact of transgenic expression, and that UCP3 does not catalyze the basal proton conductance of skeletal muscle mitochondria in the absence of activators such as superoxide.
Authors:
Susana Cadenas; Karim S Echtay; James A Harper; Mika B Jekabsons; Julie A Buckingham; Evelyn Grau; Alejandro Abuin; Helen Chapman; John C Clapham; Martin D Brand
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2001-11-13
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-21     Completed Date:  2002-02-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2773-8     Citation Subset:  IM    
Affiliation:
Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Body Weight
Carrier Proteins / biosynthesis*,  genetics*
Humans
Ion Channels
Kinetics
Mice
Mice, Knockout
Mice, Transgenic
Mitochondria / metabolism*
Mitochondrial Proteins
Muscle, Skeletal / metabolism*
Oxygen / metabolism
Oxygen Consumption
Phosphorylation
Protein Binding
Protons*
Succinic Acid / metabolism
Superoxides / metabolism
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Ion Channels; 0/Mitochondrial Proteins; 0/Protons; 0/mitochondrial uncoupling protein 3; 110-15-6/Succinic Acid; 11062-77-4/Superoxides; 7782-44-7/Oxygen

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


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