PUBLICATION
CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis
- Authors
- Li, 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.
- ID
- ZDB-PUB-140513-139
- Date
- 2014
- Source
- Biochimica et biophysica acta. Molecular basis of disease 1842(7): 1121-9 (Journal)
- Registered Authors
- Liu, Mugen, Yin, Zhan, Zhang, Jing
- Keywords
- Apoptosis, CERKL, Oxidative stress, Retina, TRX2
- MeSH Terms
-
- Animals
- Apoptosis/genetics*
- Cell Death/genetics
- Humans
- Mice
- Mitochondria/genetics*
- Mitochondria/metabolism
- Mitochondrial Proteins/genetics
- Mitochondrial Proteins/metabolism*
- NIH 3T3 Cells
- Oxidation-Reduction
- Oxidative Stress/genetics*
- Phosphotransferases (Alcohol Group Acceptor)/genetics
- Phosphotransferases (Alcohol Group Acceptor)/metabolism*
- Retina/metabolism*
- Retina/pathology*
- Thioredoxins/genetics
- Thioredoxins/metabolism*
- Zebrafish
- PubMed
- 24735978 Full text @ BBA Molecular Basis of Disease
Citation
Li, 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. Molecular basis of disease. 1842(7):1121-9.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping