title: CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Mi
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Fulton
authors.initials: F
authors.lastname: Wong
authors.affiliation: 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.
authors.forename: Xuexue
authors.initials: X
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xiukun
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Medical Genetics, Wuhan University School of Medicine, Wuhan, Hubei, PR China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jiuxiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Liao
authors.affiliation: 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.
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Hu
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, UK.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Shu
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, PR China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Yin
authors.affiliation: 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. Electronic address: zh_tang@163.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: 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. Electronic address: lium@mail.hust.edu.cn.
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000473:pathology*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D024101:Mitochondrial Proteins; C467002:TXN2 protein, human; D013879:Thioredoxins; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase
keywords: Apoptosis; CERKL; Oxidative stress; Retina; TRX2