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Fatty acids induce a conformational change in UCP1 and UCP3 in brown adipose tissue mitochondria
Author(s) -
Divakaruni Ajit,
Humphrey Dickon M.,
Brand Martin D.
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.lb149
Subject(s) - thermogenin , ucp3 , brown adipose tissue , uncoupling protein , biochemistry , mitochondrion , proteolysis , chemistry , adipose tissue , fatty acid , enzyme
In brown adipose tissue (BAT) mitochondria, uncoupling protein 1 (UCP1) dissipates the protonmotive force to generate heat. UCP1 is activated by fatty acids and inhibited by nucleotides such as GDP, but the precise mechanisms involved remain controversial. Even less is known about the physiological role and regulation of uncoupling protein 3 (UCP3) in BAT. Here we present the first demonstration of a conformational change induced by fatty acids for both UCP1 and UCP3 in rat BAT mitochondria. Conformational changes were inferred from the kinetics of proteolysis when isolated mitochondria were treated with exogenous trypsin. Palmitate increased the rate of proteolysis for both proteins, showing that palmitate binds and affects their conformation. Trypsinolysis of UCP1 could be fully rescued by GDP, consistent with its ability to compete functionally with fatty acids. However, UCP3 degradation was GDP‐independent, suggesting that GDP interacts differently (or not at all) with UCP3. Further evidence for an acute interaction between fatty acids and UCP1 was provided by altered binding of the fluorescently tagged nucleotide derivative mant‐GDP to UCP1 in the presence of palmitate. Supported by a British Marshall Scholarship and NSF Graduate Research Fellowship (ASD), the UK Medical Research Council, and the Buck Institute for Age Research.