Binding of fatty acids to the uncoupling protein from brown adipose tissue mitochondria - PubMed (original) (raw)
Binding of fatty acids to the uncoupling protein from brown adipose tissue mitochondria
Shu-Gui Huang. Arch Biochem Biophys. 2003.
Abstract
The uncoupling protein 1 (UCP1) is a H(+) carrier which plays a key role in heat generation in brown adipose tissue. The H(+) transport activity of UCP1 is activated by long-chain fatty acids and inhibited by purine nucleotides. While nucleotide binding has been well characterized, the interaction of fatty acid with UCP1 remains unknown. Here I demonstrate the binding of fatty acids by competition with a fluorescent nucleotide probe 2(')-O-dansyl guanosine 5(')-triphosphate (GTP), which has been shown previously to bind at the nucleotide binding site in UCP1. Fatty acids but not their esters competitively inhibit the binding of 2(')-O-dansyl GTP to UCP1. The fatty acid effect was enhanced at higher pH, suggesting the binding of fatty acid anion to UCP1. The inhibition constants K(i) were determined by fluorescence titrations for various fatty acids. Short-chain (C<8) fatty acids display no affinity, whereas medium-chain (C10-14) and unsaturated C18 fatty acids exhibit stronger affinity (K(i)=65 microM, for elaidic acid). This specificity profile agrees with previous functional data obtained in both proteoliposomes and mitochondria, suggesting a possible physiological role of this fatty acid binding site.
Similar articles
- The uncoupling protein UCP1 does not increase the proton conductance of the inner mitochondrial membrane by functioning as a fatty acid anion transporter.
González-Barroso MM, Fleury C, Bouillaud F, Nicholls DG, Rial E. González-Barroso MM, et al. J Biol Chem. 1998 Jun 19;273(25):15528-32. doi: 10.1074/jbc.273.25.15528. J Biol Chem. 1998. PMID: 9624141 - Mutagenesis of the uncoupling protein of brown adipose tissue. Neutralization Of E190 largely abolishes pH control of nucleotide binding.
Echtay KS, Bienengraeber M, Klingenberg M. Echtay KS, et al. Biochemistry. 1997 Jul 8;36(27):8253-60. doi: 10.1021/bi970513r. Biochemistry. 1997. PMID: 9204870 - Fatty acid interaction with mitochondrial uncoupling proteins.
Jezek P. Jezek P. J Bioenerg Biomembr. 1999 Oct;31(5):457-66. doi: 10.1023/a:1005496306893. J Bioenerg Biomembr. 1999. PMID: 10653474 Review. - Uncoupling proteins--how do they work and how are they regulated.
Klingenberg M. Klingenberg M. IUBMB Life. 2001 Sep-Nov;52(3-5):175-9. doi: 10.1080/15216540152845975. IUBMB Life. 2001. PMID: 11798030 Review.
Cited by
- A new, powerful player in lipoprotein metabolism: brown adipose tissue.
Bartelt A, Merkel M, Heeren J. Bartelt A, et al. J Mol Med (Berl). 2012 Aug;90(8):887-93. doi: 10.1007/s00109-012-0858-3. Epub 2012 Jan 10. J Mol Med (Berl). 2012. PMID: 22231746 Review. - Induction of thermogenic adipocytes: molecular targets and thermogenic small molecules.
Song NJ, Chang SH, Li DY, Villanueva CJ, Park KW. Song NJ, et al. Exp Mol Med. 2017 Jul 7;49(7):e353. doi: 10.1038/emm.2017.70. Exp Mol Med. 2017. PMID: 28684864 Free PMC article. Review. - Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria.
Fedorenko A, Lishko PV, Kirichok Y. Fedorenko A, et al. Cell. 2012 Oct 12;151(2):400-13. doi: 10.1016/j.cell.2012.09.010. Cell. 2012. PMID: 23063128 Free PMC article. - Synergy of fatty acid and reactive alkenal activation of proton conductance through uncoupling protein 1 in mitochondria.
Esteves TC, Parker N, Brand MD. Esteves TC, et al. Biochem J. 2006 May 1;395(3):619-28. doi: 10.1042/BJ20052004. Biochem J. 2006. PMID: 16451125 Free PMC article. - UCP1: A transporter for H+ and fatty acid anions.
Bertholet AM, Kirichok Y. Bertholet AM, et al. Biochimie. 2017 Mar;134:28-34. doi: 10.1016/j.biochi.2016.10.013. Epub 2016 Oct 27. Biochimie. 2017. PMID: 27984203 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials