| RRC ID |
53290
|
| 著者 |
Lin JLJ, Nakagawa A, Skeen-Gaar R, Yang WZ, Zhao P, Zhang Z, Ge X, Mitani S, Xue D, Yuan HS.
|
| タイトル |
Oxidative Stress Impairs Cell Death by Repressing the Nuclease Activity of Mitochondrial Endonuclease G.
|
| ジャーナル |
Cell Rep
|
| 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.
|
| 巻・号 |
16(2)
|
| ページ |
279-287
|
| 公開日 |
2016-7-12
|
| DOI |
10.1016/j.celrep.2016.05.090
|
| PII |
S2211-1247(16)30703-3
|
| PMID |
27346342
|
| PMC |
PMC5483177
|
| MeSH |
Animals
Apoptosis*
Caenorhabditis elegans / cytology
Caenorhabditis elegans / enzymology*
Caenorhabditis elegans Proteins / chemistry
Caenorhabditis elegans Proteins / metabolism*
Crystallography, X-Ray
Down-Regulation
Endodeoxyribonucleases / chemistry
Endodeoxyribonucleases / metabolism*
Enzyme Stability
Mitochondrial Proteins / chemistry
Mitochondrial Proteins / metabolism*
Models, Molecular
Oxidation-Reduction
Oxidative Stress*
Protein Interaction Domains and Motifs
Protein Multimerization
Protein Structure, Quaternary
|
| IF |
8.109
|
| 引用数 |
11
|
| リソース情報 |
| 線虫 |
tm1159 |
