Chemistry & Biology
Uncoupling Protein Inhibitors
the fluorescence was analyzed using an EPICS XL flow cytometer. Cells
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J.M., and Avila, M.A. (1998). Transformed but not normal hepatocytes express
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treated for 1 hr with 10 mM rotenone were used as control.
Couplan, E., Gonzalez-Barroso, M.M., Alves-Guerra, M.C., Ricquier, D.,
Goubern, M., and Bouillaud, F. (2002). No evidence for a basal, retinoic, or
superoxide-induced uncoupling activity of the uncoupling protein 2 present
in spleen or lung mitochondria. J. Biol. Chem. 277, 26268–26275.
Statistical Analysis
All values are expressed as mean SEM of at least three independent exper-
iments performed in triplicate. Differences between groups were determined
using either two-tailed unpaired Student’s t tests or the one-way ANOVA
test using the SigmaPlot software. Significant differences between groups
are indicated as *p < 0.05, **p < 0.01, and ***p < 0.001.
Derdak, Z., Mark, N.M., Beldi, G., Robson, S.C., Wands, J.R., and Baffy, G.
(2008). The mitochondrial uncoupling protein-2 promotes chemoresistance
in cancer cells. Cancer Res. 68, 2813–2819.
Echtay, K.S. (2007). Mitochondrial uncoupling proteins—what is their physio-
SUPPLEMENTAL INFORMATION
logical role? Free Radic. Biol. Med. 43, 1351–1371.
Supplemental Information includes Supplemental Experimental Procedures
and four figures and can be found with this article online at doi:10.1016/j.
Echtay, K.S., Roussel, D., St-Pierre, J., Jekabsons, M.B., Cadenas, S., Stuart,
J.A., Harper, J.A., Roebuck, S.J., Morrison, A., Pickering, S., et al. (2002).
Superoxide activates mitochondrial uncoupling proteins. Nature 415, 96–99.
Echtay, K.S., Esteves, T.C., Pakay, J.L., Jekabsons, M.B., Lambert, A.J.,
Portero-Otı´n, M., Pamplona, R., Vidal-Puig, A.J., Wang, S., Roebuck, S.J.,
and Brand, M.D. (2003). A signalling role for 4-hydroxy-2-nonenal in regulation
of mitochondrial uncoupling. EMBO J. 22, 4103–4110.
ACKNOWLEDGMENTS
This work was supported by project grants of the Spanish Ministry of Science
and Innovation (SAF2009-07126, Consolider-Ingenio 2010 CSD2007-00020,
and CTQ 2009-07752), CSIC (2004 2 0E 238), and Comunidad de Madrid
(S-SAL-0249-2006). We also thank the Ministry of Education for a doctoral
Gonza´ lez-Barroso, M.M., Fleury, C., Bouillaud, F., Nicholls, D.G., and Rial, E.
(1998). The uncoupling protein UCP1 does not increase the proton conduc-
tance of the inner mitochondrial membrane by functioning as a fatty acid anion
transporter. J. Biol. Chem. 273, 15528–15532.
´
fellowship to E.C. M.M.G.B. was supported by the ‘‘Ramon y Cajal’’ program.
The expert technical assistance of Pilar Zaragoza is gratefully acknowledged.
´
´
Gonzalez-Barroso, M.M., Fleury, C., Jimenez, M.A., Sanz, J.M., Romero, A.,
Bouillaud, F., and Rial, E. (1999). Structural and functional study of a conserved
region in the uncoupling protein UCP1: the three matrix loops are involved in
the control of transport. J. Mol. Biol. 292, 137–149.
Received: July 30, 2010
Revised: November 15, 2010
Accepted: December 6, 2010
Published: February 24, 2011
Harper, M.E., Antoniou, A., Villalobos-Menuey, E., Russo, A., Trauger, R.,
Vendemelio, M., George, A., Bartholomew, R., Carlo, D., Shaikh, A., et al.
(2002). Characterization of a novel metabolic strategy used by drug-resistant
tumor cells. FASEB J. 16, 1550–1557.
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Chemistry & Biology 18, 264–274, February 25, 2011 ª2011 Elsevier Ltd All rights reserved 273