Novel Uncoupling Proteins

Charles Affourtit, Paul G. Crichton, Nadeene Parker, Martin D. Brand

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Mitochondria are incompletely coupled because of proton leaks that shortcircuit 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 β cells, where it attenuates insulin secretion. Other roles remain to be discovered.

Original languageEnglish
Title of host publicationMitochondrial Biology: New Perspectives
Subtitle of host publicationNovartis Foundation Symposium 287
EditorsDerek J. Chadwick, Jamie Goode
PublisherWiley
Pages70-80
Number of pages11
Volume287
ISBN (Electronic)9780470725207
ISBN (Print)9780470066577
DOIs
Publication statusPublished - 5 Oct 2007

Publication series

NameNovartis Foundation Symposia
PublisherWiley

Keywords

  • Mitochondrial proton leak
  • Uncoupling proteins
  • Mild uncoupling
  • Reactive oxygen species
  • Oxidative damage
  • Degenerative disease
  • Ageing
  • Pancreatic beta cells
  • Insulin secretion

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