CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis
CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis
复制标题
CERKL 与线粒体 TRX2 相互作用，保护视网膜细胞免受氧化应激诱导的细胞凋亡。
DOI：
10.1016/j.bbadis.2014.04.009
复制
发表时间：
2014-07-01
影响因子：
6.2
通讯作者：
Liu, Mugen
中科院分区：
文献类型：
--
作者：
Li, Chang;Wang, Lei;Liu, Mugen
神经酰胺激酶样基因（CERKL）的突变与严重的视网膜变性有关。然而，编码蛋白（CERKL）的确切功能仍然未知。在这里，我们表明，CERKL与线粒体硫氧还蛋白2（TRX2）相互作用，并保持TRX2在还原的氧化还原状态。CERKL的过表达保护细胞在氧化应激下免于凋亡，而抑制CERKL使细胞对氧化应激更敏感。在斑马鱼中，CERKL蛋白主要定位于视网膜光感受器的外节和内节。斑马鱼中CERKL的敲低导致视网膜细胞死亡增加，包括视锥和视杆光感受器变性。在CERKL缺乏的斑马鱼视网膜中也检测到大分子氧化损伤的迹象。我们的研究结果表明，CERKL与TRX2相互作用，并在TRX2抗氧化途径的调节中发挥新的关键作用，并首次解释了CERKL突变如何导致视网膜细胞死亡。(C)2014爱思唯尔有限公司版权所有。
Mutations in the ceramide kinase-like gene (CERKL) are associated with severe retinal degeneration. However, the exact function of the encoded protein (CERKL) remains unknown. Here we show that CERKL interacts with mitochondrial thioredoxin 2 (TRX2) and maintains TRX2 in the reduced redox state. Overexpression of CERKL protects cells from apoptosis under oxidative stress, whereas suppressing CERKL renders cells more sensitive to oxidative stress. In zebrafish, CERKL protein prominently locates in the outer segment and inner segment of the photoreceptor of the retina. Knockdown of CERKL in the zebrafish leads to an increase of retinal cell death, including cone and rod photoreceptor degeneration. Signs of oxidative damage to macromolecules were also detected in CERKL deficient zebrafish retina. Our results show that CERKL interacts with TRX2 and plays a novel key role in the regulation of the TRX2 antioxidant pathway and, for the first time, provides an explanation of how mutations in CERKL may lead to retinal cell death. (C) 2014 Elsevier B.V. All rights reserved.