No evidence for a basal, retinoic, or superoxide-induced uncoupling activity of the uncoupling protein 2 present in spleen or lung mitochondria.
The phenotypes observed in mice whose uncoupling protein (Ucp2) gene had been invalidated by homologous recombination (Ucp2(-/-) mice) are consistent with an increase in mitochondrial membrane potential in macrophages and pancreatic beta cells. This could support an uncoupling (proton transport) activity of UCP2 in the inner mitochondrial membrane in vivo. We used mitochondria from lung or spleen, the two organs expressing the highest level of UCP2, to compare the proton leak of the mitochondrial inner membrane of wild-type and Ucp2(-/-) mice. No difference was observed under basal conditions. Previous reports have concluded that retinoic acid and superoxide activate proton transport by UCP2. Spleen mitochondria showed a higher sensitivity to retinoic acid than liver mitochondria, but this was not caused by UCP2. In contrast with a previous report, superoxide failed to increase the proton leak rate in kidney mitochondria, where no UCP2 expression was detected, and also in spleen mitochondria, which does not support stimulation of UCP2 uncoupling activity by superoxide. Finally, no increase in the ATP/ADP ratio was observed in spleen or lung of Ucp2(-/-) mice. Therefore, no evidence could be gathered for the uncoupling activity of the UCP2 present in spleen or lung mitochondria. Although this may be explained by difficulties with isolated mitochondria, it may also indicate that UCP2 has another physiological significance in spleen and lung.
Couplan
Elodie
E
Ceremod CNRS UPR9078, 9 rue Jules Hetzel, Meudon 92190, France.
del Mar Gonzalez-Barroso
Maria
M
Alves-Guerra
Marie Clotilde
MC
Ricquier
Daniel
D
Goubern
Marc
M
Bouillaud
Frédéric
F
D000818:Animals; D005434:Flow Cytometry; D007473:Ion Channels; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins; D010101:Oxygen Consumption / Q000187:drug effects; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020112:Rhodamine 123 / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D013481:Superoxides; D020112:Rhodamine 123; D014212:Tretinoin