Redox signaling (cross-talk) from and to mitochondria involves mitochondrial pores and reactive oxygen species
Redox signaling (cross-talk) from and to mitochondria involves mitochondrial pores and reactive oxygen species
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DOI：
10.1016/j.bbabio.2010.01.032
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发表时间：
2010-06-01
影响因子：
4.3
通讯作者：
Daiber, Andreas
中科院分区：
文献类型：
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作者：
Daiber, Andreas
这篇综述强调了线粒体和 NADPH 氧化酶之间氧化还原信号传导的重要作用。除了氧化还原信号传导的定义和一般重要性之外，线粒体之间的串扰！基于 4 个不同示例讨论了 Nox 衍生的活性氧 (ROS)。在第一个模型中，血管紧张素-II 被讨论为 NADPH 氧化酶激活的触发因素，随后 ROS 依赖性地打开线粒体 ATP 敏感钾通道，导致线粒体膜电位去极化，随后导致线粒体 ROS 形成和呼吸功能障碍。这一观点得到了溴化乙锭诱导的线粒体损伤抑制血管紧张素 II 依赖性 Nox1 和氧化应激增加的观察结果的支持。在另一个例子中，缺氧被用作线粒体 ROS 形成的刺激剂，并通过使用药理学和遗传抑制剂，证明了线粒体 ROS 通过 PKC epsilon 诱导 NADPH 氧化酶的作用。第三个模型基于血清撤除引起的细胞死亡，通过刺激线粒体和 Nox1 促进人类 293T 细胞中 ROS 的产生。通过卓越的分子生物学方法，作者表明，线粒体是 ROS 快速形成的原因，随后是基于响应线粒体 ROS 快速形成而激活 NADPH 氧化酶 (Nox1) 的较慢但持久的氧化应激条件。最后，在涉及线粒体通透性转换孔和 ATP 敏感钾通道的硝酸甘油诱导耐受中，显示了线粒体和 NADPH 氧化酶 (Nox2) 之间的串扰。简要讨论了这些氧化还原信号通路作为药理学靶点的用途。 (C) 2010 Elsevier B.V. 保留所有权利。
This review highlights the important role of redox signaling between mitochondria and NADPH oxidases. Besides the definition and general importance of redox signaling, the cross-talk between mitochondria! and Nox-derived reactive oxygen species (ROS) is discussed on the basis of 4 different examples. In the first model, angiotensin-II is discussed as a trigger for NADPH oxidase activation with subsequent ROS-dependent opening of mitochondrial ATP-sensitive potassium channels leading to depolarization of mitochondrial membrane potential followed by mitochondrial ROS formation and respiratory dysfunction. This concept was supported by observations that ethidium bromide-induced mitochondrial damage suppressed angiotensin-II-dependent increase in Nox1 and oxidative stress. In another example hypoxia was used as a stimulator of mitochondrial ROS formation and by using pharmacological and genetic inhibitors, a role of mitochondrial ROS for the induction of NADPH oxidase via PKC epsilon was demonstrated. The third model was based on cell death by serum withdrawal that promotes the production of ROS in human 293T cells by stimulating both the mitochondria and Nox1. By superior molecular biological methods the authors showed that mitochondria were responsible for the fast onset of ROS formation followed by a slower but long-lasting oxidative stress condition based on the activation of an NADPH oxidase (Nox1) in response to the fast mitochondrial ROS formation. Finally, a cross-talk between mitochondria and NADPH oxidases (Nox2) was shown in nitroglycerin-induced tolerance involving the mitochondrial permeability transition pore and ATP-sensitive potassium channels. The use of these redox signaling pathways as pharmacological targets is briefly discussed. (C) 2010 Elsevier B.V. All rights reserved.