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
- Enzyme Stability
- Apoptosis
- Quaternary
- Protein Multimerization
- Oxidative Stress
- X-Ray
- Endodeoxyribonucleases
- Models
- Protein Interaction Domains and Motifs
- Molecular
- Caenorhabditis elegans
- Down-Regulation
- Animals
- Mitochondrial Proteins
- Crystallography
- Caenorhabditis elegans Proteins
- Oxidation-Reduction
- Protein Structure
- Last Modified
- 2019-12-05
- Identifier
- PubMed ID: 27346342
- Resource Type
- Rights Statement
- DOI
- ISSN
- 2211-1247
- Language
Relationships
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oxidativeStressImpairsCellDeathByRepressingTheNucleaseAc.pdf | 2019-12-05 | Public | Download |