Uncoupling proteins (UCPs) are thought to be intricately controlled uncouplers1,2,3 that are responsible for the futile dissipation of mitochondrial chemiosmotic gradients, producing heat rather than ATP. They occur in many animal and plant cells4,5,6,7,8,9 and form a subfamily of the mitochondrial carrier family10. Physiological uncoupling of oxidative phosphorylation must be strongly regulated to avoid deterioration of the energy supply and cell death, which is caused by toxic uncouplers. However, an H+ transporting uncoupling function is well established only for UCP1 from brown adipose tissue2,8,9,11, and the regulation of UCP1 by fatty acids, nucleotides and pH remains controversial2,12,13,14. The failure of UCP1 expressed in Escherichia coli inclusion bodies to carry out fatty-acid-dependent H+ transport activity inclusion bodies15 made us seek a native UCP cofactor. Here we report the identification of coenzyme Q (ubiquinone) as such a cofactor. On addition of CoQ10 to reconstituted UCP1 from inclusion bodies, fatty-acid-dependent H+ transport reached the same rate as with native UCP1. The H+ transport was highly sensitive to purine nucleotides, and activated only by oxidized but not reduced CoQ. H+ transport of native UCP1 correlated with the endogenous CoQ content.
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We thank K. Beyer for the NMR measurements. This work was supported by a grant from the Deutsche Forschungsgemeinschaft.
Institute of Physiological Chemistry, University of Munich, Schillerstrasse 44, Munich, D-80336, Germany
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