ZFIN ID: ZDB-PUB-140513-139
CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis
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.
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
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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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