Expression of UCP3 in CHO cells does not cause uncoupling, but controls mitochondrial activity in the presence of glucose.
The proton-transport activity of UCP1 (uncoupling protein 1) triggers mitochondrial uncoupling and thermogenesis. The exact role of its close homologues, UCP2 and UCP3, is unclear. Mounting evidence associates them with the control of mitochondrial superoxide production. Using CHO (Chinese-hamster ovary) cells stably expressing UCP3 or UCP1, we found no evidence for respiration uncoupling. The explanation lies in the absence of an appropriate activator of UCP protonophoric function. Accordingly, the addition of retinoic acid uncouples the respiration of the UCP1-expressing clone, but not that of the UCP3-expressing ones. In a glucose-containing medium, the extent of the hyperpolarization of mitochondria by oligomycin was close to 22 mV in the five UCP3-expressing clones, contrasting with the variable values observed with the 15 controls. Our observations suggest that, when glycolysis and mitochondria generate ATP, and in the absence of appropriate activators of proton transport, UCPs do not transport protons (uncoupling), but rather other ions of physiological relevance that control mitochondrial activity. A model is proposed using the known passive transport of pyruvate by UCP1.
Mozo
Julien
J
BIOTRAM (Transporteurs Mitochondriaux et Métabolisme) CNRS UPR9078, Faculté de Médecine René Descartes Paris 5, site Necker, 156 rue de Vaugirard 75730 Paris, France.
Ferry
Gilles
G
Studeny
Aurélie
A
Pecqueur
Claire
C
Rodriguez
Marianne
M
Boutin
Jean A
JA
Bouillaud
Frédéric
F
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins; D009840:Oligomycins / Q000494:pharmacology; D010101:Oxygen Consumption; D013481:Superoxides / Q000378:metabolism; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009840:Oligomycins; C000604371:UCP1 protein, human; C000604392:UCP3 protein, human; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3; D013481:Superoxides; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005947:Glucose