Topic
UCP3
About: UCP3 is a research topic. Over the lifetime, 633 publications have been published within this topic receiving 48394 citations. The topic is also known as: uncoupling protein 3 (mitochondrial, proton carrier) & SLC25A9.
Papers published on a yearly basis
Papers
TL;DR: The discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid identity to UCP1, is reported, and properties consistent with a role in diabetes and obesity are described, suggesting that U CP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli.
Abstract: A mitochondrial protein called uncoupling protein (UCP1) plays an important role in generating heat and burning calories by creating a pathway that allows dissipation of the proton electrochemical gradient across the inner mitochondrial membrane in brown adipose tissue, without coupling to any other energy-consuming process. This pathway has been implicated in the regulation of body temperature, body composition and glucose metabolism. However, UCP1-containing brown adipose tissue is unlikely to be involved in weight regulation in adult large-size animals and humans living in a thermoneutral environment (one where an animal does not have to increase oxygen consumption or energy expenditure to lose or gain heat to maintain body temperature), as there is little brown adipose tissue present. We now report the discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid identity to UCP1, and describe properties consistent with a role in diabetes and obesity. In comparison with UCP1, UCP2 has a greater effect on mitochondrial membrane potential when expressed in yeast. Compared to UCP1, the gene is widely expressed in adult human tissues, including tissues rich in macrophages, and it is upregulated in white fat in response to fat feeding. Finally, UCP2 maps to regions of human chromosome 11 and mouse chromosome 7 that have been linked to hyperinsulinaemia and obesity. Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli.
1,752 citations
TL;DR: It is shown that superoxide increases mitochondrial proton conductance through effects on UCP1, UCP2 and UCP3, indicating that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria.
Abstract: Uncoupling protein 1 (UCP1) diverts energy from ATP synthesis to thermogenesis in the mitochondria of brown adipose tissue by catalysing a regulated leak of protons across the inner membrane. The functions of its homologues, UCP2 and UCP3, in other tissues are debated. UCP2 and UCP3 are present at much lower abundance than UCP1, and the uncoupling with which they are associated is not significantly thermogenic. Mild uncoupling would, however, decrease the mitochondrial production of reactive oxygen species, which are important mediators of oxidative damage. Here we show that superoxide increases mitochondrial proton conductance through effects on UCP1, UCP2 and UCP3. Superoxide-induced uncoupling requires fatty acids and is inhibited by purine nucleotides. It correlates with the tissue expression of UCPs, appears in mitochondria from yeast expressing UCP1, and is absent in skeletal muscle mitochondria from UCP3 knockout mice. Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria.
1,449 citations
TL;DR: In this article, the role of UCP in the regulation of body mass was determined by targeted inactivation of the gene encoding it, and it was found that UCP-deficient mice consume less oxygen after treatment with a β3-adrenergic-receptor agonist and are sensitive to cold, indicating that their thermo-regulation is defective.
Abstract: The mitochondrial uncoupling protein (UCP) in the mitochondrial inner membrane of mammalian brown adipose tissue generates heat by uncoupling oxidative phosphorylation1. This process protects against cold2 and regulates energy balance3. Manipulation of thermogenesis could be an effective strategy against obesity4–9. Here we determine the role of UCP in the regulation of body mass by targeted inactivation of the gene encoding it. We find that UCP-deficient mice consume less oxygen after treatment with a β3-adrenergic-receptor agonist and that they are sensitive to cold, indicating that their thermo-regulation is defective. However, this deficiency caused neither hyperphagia nor obesity in mice fed on either a standard or a high-fat diet. We propose that the loss of UCP may be compensated by UCP2, a newly discovered homologue of UCP; this gene is ubiquitously expressed and is induced in the brown fat of UCP-deficient mice.
1,413 citations
TL;DR: It is demonstrated here that mice lacking Ucp2 following targeted gene disruption are not obese and have a normal response to cold exposure or high-fat diet and a role for UCP2 in the limitation of ROS and macrophage-mediated immunity is indicated.
Abstract: The gene Ucp2 is a member of a family of genes found in animals and plants, encoding a protein homologous to the brown fat uncoupling protein Ucp1 (refs 1–3). As Ucp2 is widely expressed in mammalian tissues4,5, uncouples respiration6 and resides within a region of genetic linkage to obesity4, a role in energy dissipation has been proposed. We demonstrate here, however, that mice lacking Ucp2 following targeted gene disruption are not obese and have a normal response to cold exposure or high-fat diet. Expression of Ucp2 is robust in spleen, lung and isolated macrophages4,5,7, suggesting a role for Ucp2 in immunity or inflammatory responsiveness4. We investigated the response to infection with Toxoplasma gondii in Ucp2−/− mice, and found that they are completely resistant to infection, in contrast with the lethality observed in wild-type littermates. Parasitic cysts and inflammation sites in brain were significantly reduced in Ucp2−/− mice (63% decrease, P<0.04). Macrophages from Ucp2 −/− mice generated more reactive oxygen species than wild-type mice (80% increase, P<0.001) in response to T. gondii, and had a fivefold greater toxoplasmacidal activity in vitro compared with wild-type mice (P<0.001 ), which was absent in the presence of a quencher of reactive oxygen species (ROS). Our results indicate a role for Ucp2 in the limitation of ROS and macrophage-mediated immunity.
1,138 citations
TL;DR: Observations suggest a hypothesis for the main, ancestral function of uncoupling proteins: to cause mild uncoupled and so diminish mitochondrial superoxide production, hence protecting against disease and oxidative damage at the expense of a small loss of energy.
1,080 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 5 |
| 2024 | 1 |
| 2023 | 12 |
| 2022 | 21 |
| 2021 | 8 |
| 2020 | 17 |