Oxidative Stress Impairs Cell Death by Repressing the Nuclease Activity of Mitochondrial Endonuclease G
Open accessAbstract
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.
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Catalytic activity of CPS-6, the C. elegans homolog of ENDOG, is boosted upon interaction with WAH-1, the worm homolog of AIF.
“the catalytic activity of CPS-6 (the homolog of ENDOG in C. elegans) is boosted upon interaction with WAH-1 (the worm homolog of AIF) [678].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [678]
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- Authors
- Lin, J. L. J., Nakagawa, A., Skeen-Gaar, R., Yang, W.-Z., Zhao, P., Zhang, Z., Ge, X., Mitani, S., Xue, D., & Yuan, H. S.
- Affiliations
- Institute of Molecular Biology, Academia Sinica (TW)
- University of Colorado Boulder (US)
- Tsinghua University (CN)
- Japan Science and Technology Agency (JP)
- National Taiwan University (TW)
- Corresponding author
- Xue, Ding
- Yuan, Hanna S.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 16
- Issue
- 2
- Pages
- 279-287
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5483177
- OpenAlex
- W2473767293
- Cited by
- 40
- References
- 29
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 11 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 1 · 2016: 2
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CU Scholar (University of Colorado Boulder) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministry of Science and Technology, Taiwan
- National Institutes of Health (R01 GM079097, R35 GM118188, R01 GM059083)
- Academia Sinica
- National Science Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- endonuclease G, oxidative stress, reactive oxygen species, apoptosis, protein dimerization, disulfide cross-linking, Caenorhabditis elegans
- MeSH terms
- Animals, Endodeoxyribonucleases, Enzyme Stability, Models, Molecular, Oxidation-Reduction, Down-Regulation, Caenorhabditis elegans, Apoptosis, Crystallography, X-Ray, Oxidative Stress, Protein Structure, Quaternary, Mitochondrial Proteins, Caenorhabditis elegans Proteins, Protein Interaction Domains and Motifs, Protein Multimerization
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