1. Biochemistry and Chemical Biology
  2. Cell Biology
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Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress

  1. Jie Wang
  2. Kristeen A Pareja
  3. Chris A Kaiser
  4. Carolyn S Sevier  Is a corresponding author
  1. Cornell University, United States
  2. Massachusetts Institute of Technology, United States
Research Article
  • Cited 58
  • Views 3,605
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Cite this article as: eLife 2014;3:e03496 doi: 10.7554/eLife.03496

Abstract

Oxidative protein folding in the endoplasmic reticulum (ER) has emerged as a potentially significant source of cellular reactive oxygen species (ROS). Recent studies suggest that levels of ROS generated as a byproduct of oxidative folding rival those produced by mitochondrial respiration. Mechanisms that protect cells against oxidant accumulation within the ER have begun to be elucidated yet many questions still remain regarding how cells prevent oxidant-induced damage from ER folding events. Here we report a new role for a central well-characterized player in ER homeostasis as a direct sensor of ER redox imbalance. Specifically we show that a conserved cysteine in the lumenal chaperone BiP is susceptible to oxidation by peroxide, and we demonstrate that oxidation of this conserved cysteine disrupts BiP's ATPase cycle. We propose that alteration of BiP activity upon oxidation helps cells cope with disruption to oxidative folding within the ER during oxidative stress.

Article and author information

Author details

  1. Jie Wang

    Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kristeen A Pareja

    Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Chris A Kaiser

    Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Carolyn S Sevier

    Cornell University, Ithaca, United States
    For correspondence
    css224@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. David Ron, University of Cambridge, United Kingdom

Publication history

  1. Received: May 28, 2014
  2. Accepted: July 20, 2014
  3. Accepted Manuscript published: July 22, 2014 (version 1)
  4. Version of Record published: August 14, 2014 (version 2)

Copyright

© 2014, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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