Uncoupling protein 1 decreases superoxide production in brown adipose tissue mitochondria.
In thermogenic brown adipose tissue, uncoupling protein 1 (UCP1) catalyzes the dissipation of mitochondrial proton motive force as heat. In a cellular environment of high oxidative capacity such as brown adipose tissue (BAT), mitochondrial uncoupling could also reduce deleterious reactive oxygen species, but the specific involvement of UCP1 in this process is disputed. By comparing brown adipose tissue mitochondria of wild type mice and UCP1-ablated litter mates, we show that UCP1 potently reduces mitochondrial superoxide production after cold acclimation and during fatty acid oxidation. We address the sites of superoxide production and suggest diminished probability of "reverse electron transport" facilitated by uncoupled respiration as the underlying mechanism of reactive oxygen species suppression in BAT. Furthermore, ablation of UCP1 represses the cold-stimulated increase of substrate oxidation normally seen in active BAT, resulting in lower superoxide production, presumably avoiding deleterious oxidative damage. We conclude that UCP1 allows high oxidative capacity without promoting oxidative damage by simultaneously lowering superoxide production.
Oelkrug
Rebecca
R
Department of Animal Physiology, Faculty of Biology, Philipps-Universität Marburg, 35043 Marburg, Germany.
Kutschke
Maria
M
Meyer
Carola W
CW
Heldmaier
Gerhard
G
Jastroch
Martin
M
D000064:Acclimatization; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D019069:Cell Respiration; D003080:Cold Temperature; D042967:Electron Transport Complex I / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006358:Hot Temperature; D007473:Ion Channels / Q000378:metabolism*; D008293:Malates / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D011522:Protons; D019289:Pyruvic Acid / Q000378:metabolism; D013379:Substrate Specificity; D013481:Superoxides / Q000378:metabolism*; D000071256:Uncoupling Protein 1
D005227:Fatty Acids; D007473:Ion Channels; D008293:Malates; D024101:Mitochondrial Proteins; D011522:Protons; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D013481:Superoxides; C030298:malic acid; D019289:Pyruvic Acid; D042967:Electron Transport Complex I
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