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Physiological Significance of Mitochondrial Uncoupling Protein 1 in the Prevention of Reactive Oxygen Species and Control of Substrate Oxidation
Author(s) -
Jastroch Martin,
Keipert Susanne,
Meyer Carola W,
Kutschke Maria,
Heldmaier Gerhard,
Klaus Susanne,
Oelkrug Rebecca
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb585
Subject(s) - thermogenin , superoxide , oxidative phosphorylation , mitochondrion , brown adipose tissue , uncoupling protein , ucp3 , reactive oxygen species , chemistry , biochemistry , thermogenesis , skeletal muscle , mitochondrial ros , microbiology and biotechnology , adipose tissue , biology , endocrinology , enzyme
The established function of mitochondrial uncoupling protein 1 in mammalian brown adipose tissue is the dissipation of proton motive force as heat. Uncoupling of respiration may also prevent mitochondrial superoxide production and ROS formation, but the involvement of UCP1 in this process is highly disputed. We here studied in isolated mitochondria a) whether the presence of endogenous uncoupling protein 1 in brown adipose tissue affects superoxide production, in particular during cold acclimation and beta oxidation, b) whether ectopically expressed UCP1 in skeletal muscle is functional and manipulates superoxide, and c) how substrate oxidation adapts to the presence of UCP1. We show that UCP1 mitigated mitochondrial superoxide rates in both tissues. In brown adipose tissue, increases of superoxide during cold acclimation and beta oxidation were blunted as compared to UCP1 knockout mice. Uncoupling alters oxidation capacities differently depending on cell‐type: While the presence of UCP1 in brown adipose tissue allows cold‐induced increase in oxidative capacity, skeletal muscle UCP1 depresses substrate oxidation. Our results demonstrate the physiological involvement of UCP1 in the regulation of mitochondrial superoxide and provide models to further investigate how uncoupling controls oxidative capacity by altering superoxide and/or cellular ATP/ADP ratios.