Fatty acids as natural uncouplers preventing generation of O(·-)2 and H2O2 by mitochondria in the resting state

Sergey S. Korshunov, Olga V. Korkina, Enno K. Ruuge, Vladimir P. Skulachev, Anatoly A. Starkov

Research output: Contribution to journalArticlepeer-review


Both natural (laurate) and artificial (m-chlorocarbonylcyanide phenylhydrazone; CCCP) uncouplers strongly inhibit O(·-)2 and H2O2 formation by rat heart mitochondria oxidizing succinate. Carboxyatractylate, an ATP/ADP antiporter inhibitor, abolishes the laurate inhibition, the CCCP inhibition being unaffected. Atractylate partially releases the inhibition by laurate and decelerates the releasing effect of carboxyatractylate. GDP is much less effective than carboxyatractylate in releasing the laurate inhibition of reactive oxygen species (ROS) formation. Micromolar laurate concentrations arresting the ROS formation cause strong inhibition of reverse electron transfer from succinate to NAD+, whereas State 4 respiration and the transmembrane electric potential difference (ΔΨ) level are affected only slightly. It is suggested that (i) free fatty acids operate as natural 'mild uncouplers' preventing the transmembrane electrochemical H+ potential difference (Δμ(H+)) from being above a threshold critical for ROS formation by complex I and, to a lesser degree, by complex III of the respiratory chain, and (ii) it is the ATP/ADP-antiporter, rather than uncoupling protein 2, that is mainly involved in this antioxidant mechanism of heart muscle mitochondria. Copyright (C) 1998 Federation of European Biochemical Societies.

Original languageEnglish (US)
Pages (from-to)215-218
Number of pages4
JournalFEBS Letters
Issue number2-3
StatePublished - Sep 18 1998
Externally publishedYes


  • ATP/ADP antiporter
  • Fatty acid
  • Heart muscle mitochondrion
  • Reactive oxygen species
  • Uncoupling protein

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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