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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited 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

Published Date

  • July 2014

Published In

Volume / Issue

  • 1842 / 7

Start / End Page

  • 1121 - 1129

PubMed ID

  • 24735978

International Standard Serial Number (ISSN)

  • 0006-3002

Digital Object Identifier (DOI)

  • 10.1016/j.bbadis.2014.04.009


  • eng

Conference Location

  • Netherlands