Specific disintegration of complex II succinate:ubiquinone oxidoreductase links pH changes to oxidative stress for apoptosis induction.
Specific disintegration of complex II succinate:ubiquinone oxidoreductase links pH changes to oxidative stress for apoptosis induction.
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DOI：
10.1038/cdd.2010.93
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发表时间：
2011-02
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
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活性氧的产生和细胞内pH值的变化是细胞凋亡过程中常见的现象。然而，人们对它们之间的相互联系知之甚少。在这里，我们表明，许多抗癌药物以及细胞因子，如FasL和TNFα引起细胞内酸化，并导致线粒体ROS的形成。平行地，我们发现线粒体呼吸复合物II的琥珀酸：泛醌氧化还原酶（SQR）活性特异性受损，而不影响该复合物作为琥珀酸脱氢酶（SDH）的第二酶活性。只有在这种结构中，复合物II才是凋亡介导剂，并产生细胞死亡的超氧化物。这是通过pHi下降实现的，pHi下降导致SDHA/SDHB亚基（其包含SDH活性）从SQR活性所需的复合物II的膜结合组分特异性解离。
The formation of reactive oxygen species (ROS) and the change of the intracellular pH are common phenomena during apoptosis. How they are interconnected, however, is poorly understood. Here we show that numerous anticancer drugs as well as cytokines such as FasL and TNFα provoke intracellular acidification and cause the formation of mitochondrial ROS. In parallel we found that the succinate:ubiquinone oxidoreductase (SQR) activity of the mitochondrial respiratory complex II is specifically impaired without affecting the second enzymatic activity of this complex as a succinate dehydrogenase (SDH). Only in this configuration is complex II an apoptosis mediator and generates superoxides for cell death. This is achieved by the pHi decline that leads to the specific dissociation of the SDHA/SDHB subunits, which encompass the SDH activity, from the membrane-bound components of complex II that are required for the SQR activity.
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影响因子：
64.8
作者：
Ishii, N;Fujii, M;Suzuki, K
通讯作者：
Suzuki, K
影响因子：
50.3
作者：
Lee, S;Nakamura, E;Schlisio, S
通讯作者：
Schlisio, S
影响因子：
4.8
作者：
LI, JF;EASTMAN, A
通讯作者：
EASTMAN, A
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4.8
作者：
Chen, Chwen-Lih;Chen, Jingfeng;Chen, Yeong-Renn
通讯作者：
Chen, Yeong-Renn
影响因子：
3
作者：
McLennan, HR;Degli Esposti, M
通讯作者：
Degli Esposti, M