CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis

Chang Lia, Lei Wang, Jing Zhang, Mi Huang, Fulton Wong, Xuexue Liu, Fei Liu, Xiukun Cui, Guohua Yang, Jiaxiang Chen, Ying Liu, Jiuxiang Wang, Shengjie Liao, Meng Gao, Xuebin Hu, Xinhua Shu, Qing Wang, Zhan Yin, Zhaohui Tang, Mugen Liu

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)1121-1129
Number of pages9
JournalBiochimica et Biophysica Acta (BBA)
Volume1842
Issue number7
DOIs
Publication statusPublished - Jul 2014

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Thioredoxins
Oxidative Stress
Apoptosis
Genes
Zebrafish
Retina
Cell Death
ceramide kinase
Retinal Cone Photoreceptor Cells
Retinal Rod Photoreceptor Cells
Retinal Degeneration
Mutation
Protein Kinases
Oxidation-Reduction
Antioxidants

Keywords

  • CERKL
  • TRX2
  • oxidative stress
  • retina
  • apoptosis

Cite this

Lia, 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. / CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis. In: Biochimica et Biophysica Acta (BBA). 2014 ; Vol. 1842, No. 7. pp. 1121-1129.
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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.",
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author = "Chang Lia and Lei Wang and Jing Zhang and Mi Huang and Fulton Wong and Xuexue Liu and Fei Liu and Xiukun Cui and Guohua Yang and Jiaxiang Chen and Ying Liu and Jiuxiang Wang and Shengjie Liao and Meng Gao and Xuebin Hu and Xinhua Shu and Qing Wang and Zhan Yin and Zhaohui Tang and Mugen Liu",
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Lia, C, Wang, L, Zhang, J, Huang, M, Wong, F, Liu, X, Liu, F, Cui, X, Yang, G, Chen, J, Liu, Y, Wang, J, Liao, S, Gao, M, Hu, X, Shu, X, Wang, Q, Yin, Z, Tang, Z & Liu, M 2014, 'CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis', Biochimica et Biophysica Acta (BBA), vol. 1842, no. 7, pp. 1121-1129. https://doi.org/10.1016/j.bbadis.2014.04.009

CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis. / Lia, 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.

In: Biochimica et Biophysica Acta (BBA), Vol. 1842, No. 7, 07.2014, p. 1121-1129.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis

AU - Lia, Chang

AU - Wang, Lei

AU - Zhang, Jing

AU - Huang, Mi

AU - Wong, Fulton

AU - Liu, Xuexue

AU - Liu, Fei

AU - Cui, Xiukun

AU - Yang, Guohua

AU - Chen, Jiaxiang

AU - Liu, Ying

AU - Wang, Jiuxiang

AU - Liao, Shengjie

AU - Gao, Meng

AU - Hu, Xuebin

AU - Shu, Xinhua

AU - Wang, Qing

AU - Yin, Zhan

AU - Tang, Zhaohui

AU - Liu, Mugen

PY - 2014/7

Y1 - 2014/7

N2 - 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.

AB - 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.

KW - CERKL

KW - TRX2

KW - oxidative stress

KW - retina

KW - apoptosis

U2 - 10.1016/j.bbadis.2014.04.009

DO - 10.1016/j.bbadis.2014.04.009

M3 - Article

VL - 1842

SP - 1121

EP - 1129

JO - Biochimica et Biophysica Acta (BBA)

JF - Biochimica et Biophysica Acta (BBA)

SN - 0006-3002

IS - 7

ER -