RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis

Duan Wu Zhang, Jing Shao, Juan Lin, Na Zhang, Bao Ju Lu, Sheng Cai Lin, Meng Qiu Dong, Jiahuai Han

Research output: Contribution to journalArticle

1029 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)332-336
Number of pages5
JournalScience
Volume325
Issue number5938
DOIs
StatePublished - Jul 17 2009

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Receptor-Interacting Protein Serine-Threonine Kinases
Energy Metabolism
Cell Death
Necrosis
Tumor Necrosis Factor-alpha
Apoptosis
NIH 3T3 Cells
Death Domain Receptors
Caspase Inhibitors
Metabolic Networks and Pathways
Protein Kinases
Reactive Oxygen Species

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Zhang, D. W., Shao, J., Lin, J., Zhang, N., Lu, B. J., Lin, S. C., ... Han, J. (2009). RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science, 325(5938), 332-336. https://doi.org/10.1126/science.1172308

RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. / Zhang, Duan Wu; Shao, Jing; Lin, Juan; Zhang, Na; Lu, Bao Ju; Lin, Sheng Cai; Dong, Meng Qiu; Han, Jiahuai.

In: Science, Vol. 325, No. 5938, 17.07.2009, p. 332-336.

Research output: Contribution to journalArticle

Zhang, DW, Shao, J, Lin, J, Zhang, N, Lu, BJ, Lin, SC, Dong, MQ & Han, J 2009, 'RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis', Science, vol. 325, no. 5938, pp. 332-336. https://doi.org/10.1126/science.1172308
Zhang, Duan Wu ; Shao, Jing ; Lin, Juan ; Zhang, Na ; Lu, Bao Ju ; Lin, Sheng Cai ; Dong, Meng Qiu ; Han, Jiahuai. / RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. In: Science. 2009 ; Vol. 325, No. 5938. pp. 332-336.
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