Article

 

Oxidative Stress Impairs Cell Death by Repressing the Nuclease Activity of Mitochondrial Endonuclease G. Public Deposited

https://scholar.colorado.edu/concern/articles/xd07gt267
Abstract
  • Endonuclease G (EndoG) is a mitochondrial protein that is released from mitochondria and relocated into the nucleus to promote chromosomal DNA fragmentation during apoptosis. Here, we show that oxidative stress causes cell-death defects in C. elegans through an EndoG-mediated cell-death pathway. In response to high reactive oxygen species (ROS) levels, homodimeric CPS-6-the C. elegans homolog of EndoG-is dissociated into monomers with diminished nuclease activity. Conversely, the nuclease activity of CPS-6 is enhanced, and its dimeric structure is stabilized by its interaction with the worm AIF homolog, WAH-1, which shifts to disulfide cross-linked dimers under high ROS levels. CPS-6 thus acts as a ROS sensor to regulate the life and death of cells. Modulation of the EndoG dimer conformation could present an avenue for prevention and treatment of diseases resulting from oxidative stress.
Creator
Date Issued
  • 2016-07-12
Academic Affiliation
Journal Title
Journal Issue/Number
  • 2
Journal Volume
  • 16
File Extent
  • 279-287
Subject
Last Modified
  • 2019-12-05
Identifier
  • PubMed ID: 27346342
Resource Type
Rights Statement
DOI
ISSN
  • 2211-1247
Language

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