Genetic and physiological analysis of the role of uncoupling proteins in human energy homeostasis

J Mol Med (Berl). 2001;79(1):48-56. doi: 10.1007/s001090000150.


The metabolic utilization of substrates results in ATP synthesis and energy loss as heat. In tissues and cells the mitochondria reoxidize reduced coenzymes and phosphorylate ADP. A significant proportion of the energy is released through thermogenesis by mitochondria. This is due to a less than perfect coupling of cellular respiration to ATP synthesis. Previous studies of brown adipocytes, which are cells specialized in regulatory thermogenesis, have shown that heat production is due to the regulated activity and synthesis of a particular proton transporter in the inner membrane of brown adipocyte mitochondria--uncoupling protein (UCP) 1. UCP homologues have recently been identified. UCP2 is widely expressed in human tissues, whereas UCP3 is expressed predominantly in human skeletal muscles. These novel UCPs represent genes which are potentially important for regulation of metabolic pathways and energy expenditure in humans. Biochemical and genetic studies support a role for these novel UCPs in metabolic regulations in humans. However, several physiological studies question such a role. Importantly, UCP2 and UCP3 seem to be able to control the activity of mitochondria in response to oxidants.

Publication types

  • Portrait
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carrier Proteins / metabolism*
  • Energy Metabolism / physiology
  • Homeostasis / physiology
  • Humans
  • Ion Channels
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Mitochondria / metabolism*
  • Mitochondrial Proteins*
  • Proteins / metabolism*
  • Research Personnel
  • Thermogenesis / physiology*
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Uncoupling Protein 3


  • Carrier Proteins
  • Ion Channels
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Proteins
  • UCP1 protein, human
  • UCP2 protein, human
  • UCP3 protein, human
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Uncoupling Protein 3