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Hydrogen peroxide induces Arl1 degradation and impairs Golgi-mediated trafficking.
Molecular Biology of the Cell ( IF 3.1 ) Pub Date : 2020-06-17 , DOI: 10.1091/mbc.e20-01-0063
Stephen C Ireland 1 , Haoran Huang 1 , Jianchao Zhang 1 , Jie Li 1 , Yanzhuang Wang 1, 2
Affiliation  

Reactive oxygen species (ROS)-induced oxidative stress has been associated with diseases such as amyotrophic lateral sclerosis, stroke, and cancer. While the effect of ROS on mitochondria and endoplasmic reticulum (ER) has been well documented, its consequence on the Golgi apparatus is less well understood. In this study, we characterized the Golgi structure and function in HeLa cells after exposure to hydrogen peroxide (H2O2), a reagent commonly used to introduce ROS to cells. Treatment of cells with 1 mM H2O2 for 10 min resulted in the degradation of Arl1 and dissociation of GRIP domain-containing proteins Golgin-97 and Golgin-245 from the trans-Golgi. This effect could be rescued by treatment of cells with a ROS scavenger N-acetyl cysteine or protease inhibitors. Structurally, H2O2 treatment reduced the number of cisternal membranes per Golgi stack, suggesting a loss of trans-Golgi cisternae. Functionally, H2O2 treatment inhibited both anterograde and retrograde protein transport, consistent with the loss of membrane tethers on the trans-Golgi cisternae. This study revealed membrane tethers at the trans-Golgi as novel specific targets of ROS in cells.

中文翻译:


过氧化氢会诱导 Arl1 降解并损害高尔基体介导的运输。



活性氧(ROS)诱导的氧化应激与肌萎缩侧索硬化症、中风和癌症等疾病有关。虽然 ROS 对线粒体和内质网 (ER) 的影响已得到充分记录,但其对高尔基体的影响尚不清楚。在这项研究中,我们表征了 HeLa 细胞接触过氧化氢 (H2O2) 后的高尔基体结构和功能,过氧化氢是一种常用于向细胞引入 ROS 的试剂。用 1 mM H2O2 处理细胞 10 分钟,导致 Arl1 降解以及含有 GRIP 结构域的蛋白 Golgin-97 和 Golgin-245 从反式高尔基体解离。这种效应可以通过用 ROS 清除剂 N-乙酰半胱氨酸或蛋白酶抑制剂处理细胞来挽救。从结构上讲,H2O2 处理减少了每个高尔基体叠层的池膜数量,表明跨高尔基体池的损失。从功能上讲,H2O2 处理抑制了顺行和逆行蛋白质转运,这与跨高尔基体池上膜系链的丧失一致。这项研究揭示了跨高尔基体的膜系链是细胞中 ROS 的新特异性靶标。
更新日期:2020-06-17
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