Uncoupling proteins: Martin Klingenberg's contributions for 40 years

Karim S. Echtay, Martin Bienengraeber, Peter Mayinger, Simone Heimpel, Edith Winkler, Doerthe Druhmann, Karina Frischmuth, Frits Kamp, Shu Gui Huang

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


The uncoupling protein (UCP1) is a proton (H+) transporter in the mitochondrial inner membrane. By dissipating the electrochemical H+ gradient, UCP1 uncouples respiration from ATP synthesis, which drives an increase in substrate oxidation via the TCA cycle flux that generates more heat. The mitochondrial uncoupling-mediated non-shivering thermogenesis in brown adipose tissue is vital primarily to mammals, such as rodents and new-born humans, but more recently additional functions in adult humans have been described. UCP1 is regulated by β-adrenergic receptors through the sympathetic nervous system and at the molecular activity level by nucleotides and fatty acid to meet thermogenesis needs. The discovery of novel UCP homologs has greatly contributed to the understanding of human diseases, such as obesity and diabetes. In this article, we review the progress made towards the molecular mechanism and function of the UCPs, in particular focusing on the influential contributions from Martin Klingenberg's laboratory. Because all members of the UCP family are potentially promising drug targets, we also present and discuss possible approaches and methods for UCP-related drug discovery.

Original languageEnglish (US)
Pages (from-to)41-55
Number of pages15
JournalArchives of Biochemistry and Biophysics
StatePublished - Nov 1 2018


  • Brown adipose tissue
  • Drug discovery
  • Mitochondria
  • Non-shivering thermogenesis
  • Obesity
  • Solute transport
  • Uncoupling protein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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