Fatty acids as natural uncouplers preventing generation of O⋅− 2 and H2O2 by mitochondria in the resting state

FEBS Letters

Korkina, Olga V²  Korshunov, Sergey S¹  Starkov, Anatoly A¹  Ruuge, Enno K²  Skulachev, Vladimir P¹ 

[1]Department of Bioenergetics, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119899, Russia

[2]Cardiology Research Center, Moscow, Russia

关键词: Reactive oxygen species;    Heart muscle mitochondrion;    Fatty acid;    ATP/ADP antiporter;    Uncoupling protein;    transmembrane electrochemical H+ potential difference;    ΔΨ;    transmembrane electric potential difference;    Atr;    atractylate;    cAtr;    carboxyatractylate;    BSA;    bovine serum albumin;    CCCP;    m-chlorocarbonylcyanide phenylhydrazone;    ROS;    reactive oxygen species;    UCP;    uncoupling protein;   

DOI  :  10.1016/S0014-5793(98)01073-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 () 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.

【 授权许可】

Unknown