Mitochondrial respiratory chain complex I is inactivated by NADPH oxidase Nox4
Mitochondrial respiratory chain complex I is inactivated by NADPH oxidase Nox4
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DOI：
10.1042/bj20121778
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发表时间：
2013-06-01
影响因子：
4.1
通讯作者：
Jansen-Duerr, Pidder
中科院分区：
文献类型：
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作者：
Koziel, Rafal;Pircher, Haymo;Jansen-Duerr, Pidder
由NADPH氧化酶产生的活性氧在细胞信号转导中起重要作用，调节细胞的增殖、存活和分化。Nox 4（NADPH氧化酶4）诱导人内皮细胞的细胞衰老;然而，Nox 4的细胞内靶点仍然难以捉摸。在本研究中，我们发现，Nox 4诱导人内皮细胞线粒体功能障碍。NOx 4耗竭引起线粒体形态改变，稳定线粒体膜电位，减少线粒体中H2 O2的产生。高分辨率呼吸测定在透化细胞结合天然PAGE表明，Nox 4特异性抑制线粒体的电子传递链复合物I的活性，这是与复合物I亚基的浓度降低。这些数据表明了一种新的途径，通过这种途径，持续的Nox 4活性降低了线粒体的功能。
ROS (reactive oxygen species) generated by NADPH oxidases play an important role in cellular signal transduction regulating cell proliferation, survival and differentiation. Nox4 (NADPH oxidase 4) induces cellular senescence in human endothelial cells; however, intracellular targets for Nox4 remained elusive. In the present study, we show that Nox4 induces mitochondria' dysfunction in human endothelial cells. Nox4 depletion induced alterations in mitochondria' morphology, stabilized mitochondrial membrane potential and decreased production of H2O2 in mitochondria. High-resolution respirometry in permeabilized cells combined with native PAGE demonstrated that Nox4 specifically inhibits the activity of mitochondria' electron transport chain complex I, and this was associated with a decreased concentration of complex I subunits. These data suggest a new pathway by which sustained Nox4 activity decreases mitochondria' function.