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Fatty acids as natural uncouplers preventing generation of O ⋅− 2 and H 2 O 2 by mitochondria in the resting state
Author(s) -
Korshunov Sergey S,
Korkina Olga V,
Ruuge Enno K,
Skulachev Vladimir P,
Starkov Anatoly A
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01073-4
Subject(s) - antiporter , chemistry , electron transport chain , mitochondrion , respiratory chain , nad+ kinase , biochemistry , oxidative phosphorylation , transmembrane protein , oxidizing agent , electron transfer , biophysics , membrane , enzyme , biology , organic chemistry , receptor
Both natural (laurate) and artificial ( m ‐chlorocarbonylcyanide phenylhydrazone; CCCP) uncouplers strongly inhibit O ⋅− 2 and H 2 O 2 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 ( ) 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.