Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases

Stéphane Dermine, Patricia Renard, Thierry Arnould

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Mitochondrial uncoupling can be defined as a dissociation between mitochondrial membrane potential generation and its use for mitochondria-dependent ATP synthesis. Although this process was originally considered a mitochondrial dysfunction, the identification of UCP-1 as an endogenous physiological uncoupling protein suggests that the process could be involved in many other biological processes. In this review, we first compare the mitochondrial uncoupling agents available in term of mechanistic and non-specific effects. Proteins regulating mitochondrial uncoupling, as well as chemical compounds with uncoupling properties are discussed. Second, we summarize the most recent findings linking mitochondrial uncoupling and other cellular or biological processes, such as bulk and specific autophagy, reactive oxygen species production, protein secretion, cell death, physical exercise, metabolic adaptations in adipose tissue, and cell signaling. Finally, we show how mitochondrial uncoupling could be used to treat several human diseases, such as obesity, cardiovascular diseases, or neurological disorders.
Original languageEnglish
Article number795
Pages (from-to)795-838
Number of pages43
Issue number8
Publication statusPublished - 30 Jul 2019


  • adipocyte browning
  • apoptosis
  • autophagy
  • cell death
  • cell signaling
  • mitochondrial uncoupling
  • oxidative stress
  • physical exercise
  • protein secretion
  • uncoupler
  • Physical exercise
  • Oxidative stress
  • Protein secretion
  • Mitochondrial uncoupling
  • Uncoupler
  • Autophagy
  • Cell signaling
  • Adipocyte browning
  • Cell death
  • Apoptosis


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