高质子势驱动线粒体中活性氧生成机制。

High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria.

作者信息

Korshunov S S, Skulachev V P, Starkov A A

机构信息

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

出版信息

FEBS Lett. 1997 Oct 13;416(1):15-8. doi: 10.1016/s0014-5793(97)01159-9.

DOI:10.1016/s0014-5793(97)01159-9

PMID:9369223

Abstract

Formation of H2O2 has been studied in rat heart mitochondria, pretreated with H2O2 and aminotriazole to lower their antioxidant capacity. It is shown that the rate of H2O2 formation by mitochondria oxidizing 6 mM succinate is inhibited by a protonophorous uncoupler, ADP and phosphate, malonate, rotenone and myxothiazol, and is stimulated by antimycin A. The effect of ADP is abolished by carboxyatractylate and oligomycin. Addition of uncoupler after rotenone induces further inhibition of H2O2 production. Inhibition of H2O2 formation by uncoupler, malonate and ADP+Pi is shown to be proportional to the delta psi decrease by these compounds. A threshold delta psi value is found, above which a very strong increase in H2O2 production takes place. This threshold slightly exceeds the state 3 delta psi level. The data obtained are in line with the concept [Skulachev, V.P., Q. Rev. Biophys. 29 (1996), 169-2021 that a high proton motive force in state 4 is potentially dangerous for the cell due to an increase in the probability of superoxide formation.

摘要

已在经过氧化氢和氨基三唑预处理以降低其抗氧化能力的大鼠心脏线粒体中研究了过氧化氢的形成。结果表明，氧化6 mM琥珀酸的线粒体产生过氧化氢的速率受到质子载体解偶联剂、ADP和磷酸盐、丙二酸、鱼藤酮和粘噻唑的抑制，并受到抗霉素A的刺激。羧基苍术苷和寡霉素可消除ADP的作用。鱼藤酮后添加解偶联剂会进一步抑制过氧化氢的产生。解偶联剂、丙二酸和ADP+Pi对过氧化氢形成的抑制作用与这些化合物引起的Δψ降低成正比。发现了一个阈值Δψ值，高于该值时过氧化氢的产生会非常强烈地增加。该阈值略超过状态3的Δψ水平。获得的数据与以下概念一致[Skulachev, V.P., Q. Rev. Biophys. 29 (1996), 169 - 2021]，即状态4中的高质子动力势由于超氧化物形成概率的增加而对细胞具有潜在危险。