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RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis.
- Source :
-
Science (New York, N.Y.) [Science] 2009 Jul 17; Vol. 325 (5938), pp. 332-6. Date of Electronic Publication: 2009 Jun 04. - Publication Year :
- 2009
-
Abstract
- Necrosis can be induced by stimulating death receptors with tumor necrosis factor (TNF) or other agonists; however, the underlying mechanism differentiating necrosis from apoptosis is largely unknown. We identified the protein kinase receptor-interacting protein 3 (RIP3) as a molecular switch between TNF-induced apoptosis and necrosis in NIH 3T3 cells and found that RIP3 was required for necrosis in other cells. RIP3 did not affect RIP1-mediated apoptosis but was required for RIP1-mediated necrosis and the enhancement of necrosis by the caspase inhibitor zVAD. By activating key enzymes of metabolic pathways, RIP3 regulates TNF-induced reactive oxygen species production, which partially accounts for RIP3's ability to promote necrosis. Our data suggest that modulation of energy metabolism in response to death stimuli has an important role in the choice between apoptosis and necrosis.
- Subjects :
- Amino Acid Chloromethyl Ketones pharmacology
Animals
Cell Line
Energy Metabolism
Glutamate Dehydrogenase metabolism
Glutamate-Ammonia Ligase metabolism
Glycogen Phosphorylase metabolism
Mice
NIH 3T3 Cells
RNA Interference
Reactive Oxygen Species metabolism
Receptor-Interacting Protein Serine-Threonine Kinases genetics
Apoptosis
Necrosis
Receptor-Interacting Protein Serine-Threonine Kinases metabolism
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 325
- Issue :
- 5938
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 19498109
- Full Text :
- https://doi.org/10.1126/science.1172308