Are mitochondrial reactive oxygen species required for autophagy?
Are mitochondrial reactive oxygen species required for autophagy?
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DOI：
10.1016/j.bbrc.2011.07.036
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发表时间：
2011-08-19
影响因子：
3.1
通讯作者：
Kagan, Valerian E.
中科院分区：
文献类型：
--
作者：
Jiang, Jianfei;Maeda, Akihiro;Ji, Jing;Baty, Catherine J.;Watkins, Simon C.;Greenberger, Joel S.;Kagan, Valerian E.
活性氧（ROS）参与自噬信号传导。支持证据被自噬和凋亡的干扰所掩盖，后者严重依赖于ROS信号传导。为了从细胞凋亡中剖析自噬，我们使用shRNA敲低HeLa细胞中细胞色素c的表达，细胞色素c是HeLa依赖性细胞凋亡的关键组分。在细胞色素c缺陷的HeLa 1.2细胞中，由于线粒体呼吸复合物III和IV之间缺乏电子穿梭，电子传递受到损害。在用星形孢菌素（STS）处理的HeLa 1.2细胞中观察到快速和稳健的LC 3-I/II转化和线粒体降解。STS处理的HeLa1.2细胞既没有产生超氧化物，也没有H2 O2的积累。膜渗透性抗氧化剂，PEG-SOD，加上过氧化氢酶STS诱导的LC 3-I/II转换和线粒体降解没有影响。此外，STS在线粒体DNA缺陷的ρ° HeLa 1.2细胞中引起自噬，其中电子传递和ROS产生都被完全破坏。与普遍的观点相反，我们得出结论，线粒体ROS不需要诱导自噬。
Reactive oxygen species (ROS) are said to participate in the autophagy signaling. Supporting evidence is obscured by interference of autophagy and apoptosis, whereby the latter heavily relies on ROS signaling. To dissect autophagy from apoptosis we knocked down expression of cytochrome c, the key component of mitochondria-dependent apoptosis, in HeLa cells using shRNA. In cytochrome c deficient HeLa1.2 cells, electron transport was compromised due to the lack of electron shuttle between mitochondrial respiratory complexes III and IV. A rapid and robust LC3-I/II conversion and mitochondria degradation were observed in HeLa1.2 cells treated with staurosporine (STS). Neither generation of superoxide nor accumulation of H2O2 was detected in STS-treated HeLa1.2 cells. A membrane permeable antioxidant, PEG-SOD, plus catalase exerted no effect on STS-induced LC3-I/II conversion and mitochondria degradation. Further, STS caused autophagy in mitochondria DNA-deficient ρ° HeLa1.2 cells in which both electron transport and ROS generation were completely disrupted. Counter to the widespread view, we conclude that mitochondrial ROS are not required for the induction of autophagy.
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影响因子：
64.8
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
14.8
作者：
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通讯作者：
Borisenko, GG
影响因子：
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作者：
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影响因子：
7.8
作者：
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通讯作者：
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影响因子：
4
作者：
Chen, Yongqiang;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.