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Mitochondrial uncoupling: role of uncoupling protein anion carriers and relationship to thermogenesis and weight control "the benefits of losing control".

Publication ,  Journal Article
Diehl, AM; Hoek, JB
Published in: J Bioenerg Biomembr
October 1999

Uncoupling proteins, a subgroup of the mitochondrial anion transporter superfamily, have been identified in prokaryotes, plants, and mammalian cells. Evolutionary conservation of these molecules reflects their importance as regulators of two critical mitochondrial functions, i.e., ATP synthesis and the production of reactive oxygen species (ROS). Although the amino acid sequences of the three mammalian uncoupling proteins, UCP1, UCP2 and UCP3, are very similar, each homolog is the product of a unique gene and important differences have been demonstrated in their tissue-specific expression and regulation. UCP1 and UCP3 appear to be key regulators of energy expenditure, and hence, nonshivering thermogenesis, either in brown adipose tissue (UCP1) or skeletal muscle (UCP3). UCP2 is expressed more ubiquitously, although generally at low levels, in many tissues. There is conflicting evidence about its importance as a regulator of resting metabolic rate. However, evidence suggests that this homolog might modulate the mitochondrial generation of ROS in some cell types, including macrophages and hepatocytes. While the induction of various uncoupling protein homologs provides adaptive advantages, both to the organism (e.g., thermogenesis) and to individual cells (e.g., reduced ROS), increased uncoupling protein activity also increases cellular vulnerability to necrosis by compromising the mitochondrial membrane potential. This narrow "risk-benefit" margin necessitates tight control of uncoupling protein activity in order to preserve cellular viability and much remains to be learned about the regulatory mechanisms involved.

Duke Scholars

Published In

J Bioenerg Biomembr

DOI

ISSN

0145-479X

Publication Date

October 1999

Volume

31

Issue

5

Start / End Page

493 / 506

Location

United States

Related Subject Headings

  • Uncoupling Protein 2
  • Uncoupling Protein 1
  • Uncoupling Agents
  • Reactive Oxygen Species
  • Proteins
  • Mitochondrial Proteins
  • Mitochondria
  • Membrane Transport Proteins
  • Membrane Proteins
  • Ion Channels
 

Citation

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Diehl, A. M., & Hoek, J. B. (1999). Mitochondrial uncoupling: role of uncoupling protein anion carriers and relationship to thermogenesis and weight control "the benefits of losing control". J Bioenerg Biomembr, 31(5), 493–506. https://doi.org/10.1023/a:1005452624640
Diehl, A. M., and J. B. Hoek. “Mitochondrial uncoupling: role of uncoupling protein anion carriers and relationship to thermogenesis and weight control "the benefits of losing control".J Bioenerg Biomembr 31, no. 5 (October 1999): 493–506. https://doi.org/10.1023/a:1005452624640.
Diehl, A. M., and J. B. Hoek. “Mitochondrial uncoupling: role of uncoupling protein anion carriers and relationship to thermogenesis and weight control "the benefits of losing control".J Bioenerg Biomembr, vol. 31, no. 5, Oct. 1999, pp. 493–506. Pubmed, doi:10.1023/a:1005452624640.
Journal cover image

Published In

J Bioenerg Biomembr

DOI

ISSN

0145-479X

Publication Date

October 1999

Volume

31

Issue

5

Start / End Page

493 / 506

Location

United States

Related Subject Headings

  • Uncoupling Protein 2
  • Uncoupling Protein 1
  • Uncoupling Agents
  • Reactive Oxygen Species
  • Proteins
  • Mitochondrial Proteins
  • Mitochondria
  • Membrane Transport Proteins
  • Membrane Proteins
  • Ion Channels