Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins.

TitleMitochondrial superoxide: production, biological effects, and activation of uncoupling proteins.
Publication TypeJournal Article
Year of Publication2004
AuthorsBrand, MD, Affourtit, C, Esteves, TC, Green, K, Lambert, AJ, Miwa, S, Pakay, JL, Parker, N
JournalFree Radic Biol Med
Volume37
Issue6
Pagination755-67
Date Published2004 Sep 15
ISSN0891-5849
KeywordsAging, Aldehydes, Animals, Carrier Proteins, Electron Transport, Fatty Acids, Free Radicals, Glucose, Humans, Insulin, Insulin Secretion, Ion Channels, Islets of Langerhans, Lipid Peroxidation, Membrane Proteins, Membrane Transport Proteins, Mice, Mice, Knockout, Mitochondria, Mitochondrial Proteins, Models, Biological, Oxygen, Protons, Signal Transduction, Superoxides, Uncoupling Protein 1, Uncoupling Protein 2, Uncoupling Protein 3
Abstract

Mitochondria are potent producers of cellular superoxide, from complexes I and III of the electron transport chain, and mitochondrial superoxide production is a major cause of the cellular oxidative damage that may underlie degradative diseases and aging. This superoxide production is very sensitive to the proton motive force, so it can be strongly decreased by mild uncoupling. Superoxide and the lipid peroxidation products it engenders, including hydroxyalkenals such as hydroxynonenal, are potent activators of proton conductance by mitochondrial uncoupling proteins such as UCP2 and UCP3, although the mechanism of activation has yet to be established. These observations suggest a hypothesis for the main, ancestral function of uncoupling proteins: to cause mild uncoupling and so diminish mitochondrial superoxide production, hence protecting against disease and oxidative damage at the expense of a small loss of energy. We review the growing evidence for this hypothesis, in mitochondria, in cells, and in vivo. More recently evolved roles of uncoupling proteins are in adaptive thermogenesis (UCP1) and perhaps as part of a signaling pathway to regulate insulin secretion in pancreatic beta cells (UCP2).

DOI10.1016/j.freeradbiomed.2004.05.034
Alternate JournalFree Radic. Biol. Med.
Citation Key10.1016/j.freeradbiomed.2004.05.034
PubMed ID15304252