6‐Ketocholestanol abolishes the effect of the most potent uncouplers of oxidative phosphorylation in mitochondria

FEBS Letters

Starkov, A.A.¹  Dedukhova, V.I.¹  Skulachev, V.P.¹ 

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

关键词: Uncoupling;    6-Ketocholestanol;    Mitochondrion;    Carboxyatractylate;    ΔΨ;    transmembrane electrical potential difference;    BSA;    bovine serum albumin;    cAtr;    carboxyatractylate;    CCCP;    carbonylcyanide-3-chlorophenylhydrazone;    Ch;    cholesterol;    DNP;    2;    4-dinitrophenol;    EGTA;    ethylene glycol-bis(β-aminoethylether)-N;    N;    N′;    N′-tetraacetic acid;    FCCP;    p-trifluoromethoxycarbonylcyanide phenylhydrazone;    kCh;    6-ketocholestanol (5α-Cholestan-3β-ol-6-one);    MOPS;    morpholinopropane sulphonate;    PMS;    phenazine methosulphate;    TPP+;    tetraphenyl phosphonium;    TTFB;    tetrachlorotrifluoromethylbenzimidazole;   

DOI  :  10.1016/0014-5793(94)01211-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effect of a keto-derivative of cholesterol, namely, 6-ketocholestanol (5α-cholestan-3β-ol-6-one; kCh) on the uncoupling of oxidation and phosphorylation by various uncouplers was studied in rat heart mitochondria. kCh was found to completely abolish the uncoupling effect (the increase in the respiration rate under the respiratory control conditions and the decrease in the membrane potential) caused of FCCP, CCCP and SF6847 and partially by TTFB at low concentrations of uncouplers. It was without effect on the uncoupling by PCP, DNP and palmitate. Carboxyatractylate, a specific inhibitor of the ADP/ATP-antiporter, was shown to almost completely abolish the uncoupling induced by palmitate and partially by low concentration of TTFB, PCP and DNP. Effects of high concentrations of all these uncouplers as well as of any concentrations of gramicidin proved to be kCh- and carboxyatractilate-insensitive. The data are discussed in terms of the hypothesis on the protein-mediated mechanism of the protonophorous uncoupling.

【 授权许可】

Unknown