Coenzyme Q is an obligatory cofactor for uncoupling protein function.
Uncoupling proteins (UCPs) are thought to be intricately controlled uncouplers that are responsible for the futile dissipation of mitochondrial chemiosmotic gradients, producing heat rather than ATP. They occur in many animal and plant cells and form a subfamily of the mitochondrial carrier family. 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 tissue, and the regulation of UCP1 by fatty acids, nucleotides and pH remains controversial. The failure of UCP1 expressed in Escherichia coli inclusion bodies to carry out fatty-acid-dependent H+ transport activity inclusion bodies 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.
Echtay
K S
KS
Institute of Physiological Chemistry, University of Munich, Germany.
Winkler
E
E
Klingenberg
M
M
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D002417:Cattle; D006224:Cricetinae; D004926:Escherichia coli; D002479:Inclusion Bodies / Q000378:metabolism; D007473:Ion Channels; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology; D024101:Mitochondrial Proteins; D011487:Protein Conformation; D011522:Protons; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D014451:Ubiquinone / Q000502:physiology*; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011522:Protons; D011994:Recombinant Proteins; D000071256:Uncoupling Protein 1; D014451:Ubiquinone