Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 6, 36
eCollection

Mitochondrial Uncoupling Proteins and Energy Metabolism

Affiliations
Review

Mitochondrial Uncoupling Proteins and Energy Metabolism

Rosa A Busiello et al. Front Physiol.

Abstract

Understanding the metabolic factors that contribute to energy metabolism (EM) is critical for the development of new treatments for obesity and related diseases. Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP synthesis, and the process of proton-leak plays a crucial role. Proton-leak accounts for a significant part of the resting metabolic rate (RMR) and therefore enhancement of this process represents a potential target for obesity treatment. Since their discovery, uncoupling proteins have stimulated great interest due to their involvement in mitochondrial-inducible proton-leak. Despite the widely accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1), which was the first in this family to be discovered, the reactions catalyzed by its homolog UCP3 and the physiological role remain under debate. This review provides an overview of the role played by UCP1 and UCP3 in mitochondrial uncoupling/functionality as well as EM and suggests that they are a potential therapeutic target for treating obesity and its related diseases such as type II diabetes mellitus.

Keywords: energy metabolism; mitochondria; obesity; proton-leak; uncoupling protein.

Figures

Figure 1
Figure 1
Schematic representation of proton-leak and of the proposed role of UCPs in influencing energy metabolism.
Figure 2
Figure 2
Schematic diagram that illustrates how the reactions influenced by UCP3 could be redirected to prevent or treat obesity, insulin resistance, and type 2 diabetes (T2DM).

Similar articles

See all similar articles

Cited by 50 articles

See all "Cited by" articles

References

    1. Adams S. H., Hoppel C. L., Lok K. H., Zhao L., Wong S. W., Minkler P. E., et al. . (2009). Plasma acylcarnitine profiles suggestincomplete long-chain fatty acid beta-oxidation and altered tricarboxylic acid cycleactivity in type 2 diabetic African-American women. J. Nutr. 139, 1073–1081. 10.3945/jn.108.103754 - DOI - PMC - PubMed
    1. Adjeitey C. N., Mailloux R. J., Dekemp R. A., Harper M. E. (2013). Mitochondrial uncoupling in skeletal muscle by UCP1 augments energy expenditure and glutathione content while mitigating ROS production. Am. J. Physiol. Endocrinol. Metab. 305, E405–E415. 10.1152/ajpendo.00057 - DOI - PMC - PubMed
    1. Aguer C., Fiehn O., Seifert E. L., Bézaire V., Meissen J. K., Daniels A., et al. . (2013). Muscle uncoupling protein 3 overexpression mimics endurance training and reduces circulating biomarkers of incomplete β-oxidation. FASEB J. 27, 4213–4225. 10.1096/fj.13-234302 - DOI - PMC - PubMed
    1. Argyropoulos G., Brown A. M., Willi S. M., Zhu J., He Y., Reitman M., et al. . (1998). Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes. J. Clin. Invest. 102, 1345–1351. 10.1172/JCI4115 - DOI - PMC - PubMed
    1. Bartelt A., Merkel M., Heeren J. (2012). A new powerful player in lipoprotein metabolism: brown adipose tissue. J Mol. Med. (Berl.) 90, 887–893. 10.1007/s00109-012-0858-3 - DOI - PubMed

LinkOut - more resources

Feedback