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

Published

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Diehl, AM; Hoek, JB

Published Date

  • October 1999

Published In

Volume / Issue

  • 31 / 5

Start / End Page

  • 493 - 506

PubMed ID

  • 10653477

Pubmed Central ID

  • 10653477

Electronic International Standard Serial Number (EISSN)

  • 1573-6881

International Standard Serial Number (ISSN)

  • 0145-479X

Digital Object Identifier (DOI)

  • 10.1023/a:1005452624640

Language

  • eng