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CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis
Li, Chang1; Wang, Lei1; Zhang, Jing1,2; Huang, Mi1; Wong, Fulton3,4; Liu, Xuexue1; Liu, Fei1; Cui, Xiukun1; Yang, Guohua5; Chen, Jiaxiang1; Liu, Ying1; Wang, Jiuxiang1; Liao, Shengjie1; Gao, Meng1; Hu, Xuebin1; Shu, Xinhua6; Wang, Qing1; Yin, Zhan7; Tang, Zhaohui1; Liu, Mugen1; Liu, MG (reprint author), Huazhong Univ Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys, Minist Educ, 1037 Luoyu Rd, Wuhan 430074, Hubei, Peoples R China.
2014-07-01
Source PublicationBIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
ISSN0925-4439
Volume1842Issue:7Pages:1121-1129
AbstractMutations 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.; 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.
SubtypeArticle
KeywordCerkl Trx2 Oxidative Stress Retina Apoptosis
Department[Li, Chang; Wang, Lei; Zhang, Jing; Huang, Mi; Liu, Xuexue; Liu, Fei; Cui, Xiukun; Chen, Jiaxiang; Liu, Ying; Wang, Jiuxiang; Liao, Shengjie; Gao, Meng; Hu, Xuebin; Wang, Qing; Tang, Zhaohui; Liu, Mugen] Huazhong Univ Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys, Coll Life Sci & Technol,Minist Educ, Wuhan 430074, Hubei, Peoples R China; [Zhang, Jing] Henan Univ, Coll Med, Inst Immunol, Key Lab Cellular & Mol Immunol, Kaifeng 475004, Henan, Peoples R China; [Wong, Fulton] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC 27710 USA; [Wong, Fulton] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA; [Yang, Guohua] Wuhan Univ, Sch Med, Dept Med Genet, Wuhan 430072, Hubei, Peoples R China; [Shu, Xinhua] Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland; [Yin, Zhan] Chinese Acad Sci, Inst Hydrobiol, Wuhan, Hubei, Peoples R China
DOI10.1016/j.bbadis.2014.04.009
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNational Natural Science Foundation of China [30771199, 81270983, 81371064]; Research Fund for the Doctoral Program of Higher Education of China [20120142110077]; Ministry of Education of the People's Republic of China [B08029]; National Key Technology R&D Program in the 12th Five year Plan of China [2012BAI09B04] ; National Natural Science Foundation of China [30771199, 81270983, 81371064]; Research Fund for the Doctoral Program of Higher Education of China [20120142110077]; Ministry of Education of the People's Republic of China [B08029]; National Key Technology R&D Program in the 12th Five year Plan of China [2012BAI09B04] ; National Natural Science Foundation of China [30771199, 81270983, 81371064]; Research Fund for the Doctoral Program of Higher Education of China [20120142110077]; Ministry of Education of the People's Republic of China [B08029]; National Key Technology R&D Program in the 12th Five year Plan of China [2012BAI09B04] ; National Natural Science Foundation of China [30771199, 81270983, 81371064]; Research Fund for the Doctoral Program of Higher Education of China [20120142110077]; Ministry of Education of the People's Republic of China [B08029]; National Key Technology R&D Program in the 12th Five year Plan of China [2012BAI09B04]
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS IDWOS:000336698400024
WOS KeywordCERAMIDE KINASE-LIKE ; RECESSIVE RETINITIS-PIGMENTOSA ; CONE-ROD DYSTROPHY ; PHOTORECEPTOR DEGENERATION ; MACULAR DEGENERATION ; ER STRESS ; THIOREDOXIN ; GENE ; DEATH ; DAMAGE
Funding OrganizationNational Natural Science Foundation of China [30771199, 81270983, 81371064]; Research Fund for the Doctoral Program of Higher Education of China [20120142110077]; Ministry of Education of the People's Republic of China [B08029]; National Key Technology R&D Program in the 12th Five year Plan of China [2012BAI09B04] ; National Natural Science Foundation of China [30771199, 81270983, 81371064]; Research Fund for the Doctoral Program of Higher Education of China [20120142110077]; Ministry of Education of the People's Republic of China [B08029]; National Key Technology R&D Program in the 12th Five year Plan of China [2012BAI09B04] ; National Natural Science Foundation of China [30771199, 81270983, 81371064]; Research Fund for the Doctoral Program of Higher Education of China [20120142110077]; Ministry of Education of the People's Republic of China [B08029]; National Key Technology R&D Program in the 12th Five year Plan of China [2012BAI09B04] ; National Natural Science Foundation of China [30771199, 81270983, 81371064]; Research Fund for the Doctoral Program of Higher Education of China [20120142110077]; Ministry of Education of the People's Republic of China [B08029]; National Key Technology R&D Program in the 12th Five year Plan of China [2012BAI09B04]
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Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/20081
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorLiu, MG (reprint author), Huazhong Univ Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys, Minist Educ, 1037 Luoyu Rd, Wuhan 430074, Hubei, Peoples R China.
Affiliation1.Huazhong Univ Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys, Coll Life Sci & Technol,Minist Educ, Wuhan 430074, Hubei, Peoples R China
2.Henan Univ, Coll Med, Inst Immunol, Key Lab Cellular & Mol Immunol, Kaifeng 475004, Henan, Peoples R China
3.Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC 27710 USA
4.Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA
5.Wuhan Univ, Sch Med, Dept Med Genet, Wuhan 430072, Hubei, Peoples R China
6.Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland
7.Chinese Acad Sci, Inst Hydrobiol, Wuhan, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Li, Chang,Wang, Lei,Zhang, Jing,et al. CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,2014,1842(7):1121-1129.
APA Li, Chang.,Wang, Lei.,Zhang, Jing.,Huang, Mi.,Wong, Fulton.,...&Liu, MG .(2014).CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,1842(7),1121-1129.
MLA Li, Chang,et al."CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1842.7(2014):1121-1129.
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