6-酮胆甾烷醇可消除线粒体中最有效的氧化磷酸化解偶联剂的作用。

6-ketocholestanol abolishes the effect of the most potent uncouplers of oxidative phosphorylation in mitochondria.

作者信息

Starkov A A, Dedukhova V I, Skulachev V P

机构信息

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

出版信息

FEBS Lett. 1994 Dec 5;355(3):305-8. doi: 10.1016/0014-5793(94)01211-3.

DOI:10.1016/0014-5793(94)01211-3

PMID:7988694

Abstract

The effect of a keto-derivative of cholesterol, namely, 6-ketocholestanol (5 alpha-cholestan-3 beta-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.

摘要

在大鼠心脏线粒体中，研究了胆固醇的一种酮衍生物，即6-酮胆甾烷醇（5α-胆甾烷-3β-醇-6-酮；kCh）对各种解偶联剂引起的氧化与磷酸化解偶联的影响。发现kCh能完全消除由FCCP、CCCP和SF6847引起的解偶联效应（在呼吸控制条件下呼吸速率增加以及膜电位降低），在低浓度解偶联剂时也能部分消除TTFB引起的解偶联效应。它对PCP、DNP和棕榈酸酯引起的解偶联没有影响。ADP/ATP反向转运体的特异性抑制剂羧基苍术苷几乎能完全消除棕榈酸酯引起的解偶联，也能部分消除低浓度TTFB、PCP和DNP引起的解偶联。所有这些高浓度解偶联剂以及任何浓度短杆菌肽的作用都被证明对kCh和羧基苍术苷不敏感。根据质子载体解偶联的蛋白质介导机制假说对这些数据进行了讨论。