Novel uncoupling proteins.

TitleNovel uncoupling proteins.
Publication TypeJournal Article
Year of Publication2007
AuthorsAffourtit, C, Crichton, PG, Parker, N, Brand, MD
JournalNovartis Found Symp
Pagination70-80; discussion 80-91
Date Published2007
KeywordsAnimals, Humans, Ion Channels, Mitochondria, Mitochondrial Proteins, Reactive Oxygen Species, Uncoupling Agents, Uncoupling Protein 1

Mitochondria are incompletely coupled because of proton leaks that short-circuit oxidative phosphorylation. Basal proton leak is unregulated and is associated with the presence (but not catalytic activity) of the adenine nucleotide translocase. Inducible proton leak is regulated and is catalysed by the adenine nucleotide translocase and specific uncoupling proteins (UCPs). UCP1 catalyses proton conductance in mammalian brown adipose tissue. It is activated by fatty acids, which overcome nucleotide inhibition. UCP2, UCP3 and UCPs from birds, fish and plants also catalyse proton conductance that is inhibited by nucleotides. However, they require activation by superoxide or other reactive oxygen species (ROS). The mechanism of proton transport by the UCPs is unresolved. UCPs may also transport fatty acids or fatty acyl peroxides. Several physiological functions of UCPs are postulated. (1) UCP1 is specialised for thermogenesis; UCP3 and avian UCPs possibly share this function. (2) UCPs may attenuate ROS production and protect against oxidative damage, degenerative diseases and ageing. (3) UCP3 may catalyse fatty acid transport. (4) UCP2 has a signalling role in pancreatic beta cells, where it attenuates insulin secretion. Other roles remain to be discovered.

Alternate JournalNovartis Found. Symp.
Citation Key742
PubMed ID18074632
Grant ListMC_U105663137 / / Medical Research Council / United Kingdom