Li Chang, Wang Lei, Zhang Jing, Huang Mi, Wong Fulton, Liu Xuexue, Liu Fei, Cui Xiukun, Yang Guohua, Chen Jiaxiang, Liu Ying, Wang Jiuxiang, Liao Shengjie, Gao Meng, Hu Xuebin, Shu Xinhua, Wang Qing, Yin Zhan, Tang Zhaohui, Liu Mugen
Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Cellular and Molecular Immunology, Institute of Immunology, Medical College of Henan University, Kaifeng, Henan 475004, PR China.
Biochim Biophys Acta. 2014 Jul;1842(7):1121-9. doi: 10.1016/j.bbadis.2014.04.009. Epub 2014 Apr 13.
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.
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）的确切功能仍不清楚。在此我们表明，CERKL与线粒体硫氧还蛋白2（TRX2）相互作用，并使TRX2维持在还原氧化状态。CERKL的过表达可保护细胞在氧化应激下免于凋亡，而抑制CERKL则使细胞对氧化应激更敏感。在斑马鱼中，CERKL蛋白主要定位在视网膜光感受器的外段和内段。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缺陷的斑马鱼视网膜中也检测到了大分子氧化损伤的迹象。我们的结果表明，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，并且首次解释了CERKL中的突变如何导致视网膜细胞死亡。
