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Energy metabolism in uncoupling protein 3 gene knockout mice.

Publication ,  Journal Article
Vidal-Puig, AJ; Grujic, D; Zhang, CY; Hagen, T; Boss, O; Ido, Y; Szczepanik, A; Wade, J; Mootha, V; Cortright, R; Muoio, DM; Lowell, BB
Published in: J Biol Chem
May 26, 2000

Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important roles in regulating energy expenditure, body weight, and thermoregulation. Other postulated roles for UCP3 include regulation of fatty acid metabolism, adaptive responses to acute exercise and starvation, and prevention of reactive oxygen species (ROS) formation. To address these questions, we have generated mice lacking UCP3 (UCP3 knockout (KO) mice). Here, we provide evidence that skeletal muscle mitochondria lacking UCP3 are more coupled (i.e. increased state 3/state 4 ratio), indicating that UCP3 has uncoupling activity. In addition, production of ROS is increased in mitochondria lacking UCP3. This study demonstrates that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS. Despite these effects on mitochondrial function, UCP3 does not seem to be required for body weight regulation, exercise tolerance, fatty acid oxidation, or cold-induced thermogenesis. The absence of such phenotypes in UCP3 KO mice could not be attributed to up-regulation of other UCP mRNAs. However, alternative compensatory mechanisms cannot be excluded. The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 26, 2000

Volume

275

Issue

21

Start / End Page

16258 / 16266

Location

United States

Related Subject Headings

  • Uncoupling Protein 3
  • Uncoupling Protein 2
  • Uncoupling Protein 1
  • Reactive Oxygen Species
  • RNA, Messenger
  • Proteins
  • Physical Conditioning, Animal
  • Phenotype
  • Oxygen Consumption
  • Muscle, Skeletal
 

Citation

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Vidal-Puig, A. J., Grujic, D., Zhang, C. Y., Hagen, T., Boss, O., Ido, Y., … Lowell, B. B. (2000). Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem, 275(21), 16258–16266. https://doi.org/10.1074/jbc.M910179199
Vidal-Puig, A. J., D. Grujic, C. Y. Zhang, T. Hagen, O. Boss, Y. Ido, A. Szczepanik, et al. “Energy metabolism in uncoupling protein 3 gene knockout mice.J Biol Chem 275, no. 21 (May 26, 2000): 16258–66. https://doi.org/10.1074/jbc.M910179199.
Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, Ido Y, et al. Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem. 2000 May 26;275(21):16258–66.
Vidal-Puig, A. J., et al. “Energy metabolism in uncoupling protein 3 gene knockout mice.J Biol Chem, vol. 275, no. 21, May 2000, pp. 16258–66. Pubmed, doi:10.1074/jbc.M910179199.
Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, Ido Y, Szczepanik A, Wade J, Mootha V, Cortright R, Muoio DM, Lowell BB. Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem. 2000 May 26;275(21):16258–16266.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 26, 2000

Volume

275

Issue

21

Start / End Page

16258 / 16266

Location

United States

Related Subject Headings

  • Uncoupling Protein 3
  • Uncoupling Protein 2
  • Uncoupling Protein 1
  • Reactive Oxygen Species
  • RNA, Messenger
  • Proteins
  • Physical Conditioning, Animal
  • Phenotype
  • Oxygen Consumption
  • Muscle, Skeletal