DOI: 10.1126/science.1172308 ISSN:

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
  • Multidisciplinary

The Grim RIPper

Cells can undergo regulated cell death through distinct processes known as apoptosis and necrosis. Regulation of apoptosis is better understood than that of necrosis. In a screen for gene products that participate in control of necrosis in cells treated with TNF (tumor necrosis factor), D.-W. Zhang et al. (p. 332 ; published online 4 June) identified a protein kinase, RIP3. In cells treated with TNF and a caspase inhibitor that inhibits apoptosis, seven metabolic enzymes interacted with RIP3, some of which are associated with mitochondria. Generation of reactive oxygen species was necessary for TNF-induced necrosis, and depletion of RIP3 reduced the generation of reactive oxygen species. Thus, RIP3 may participate in the mechanisms that link energy metabolism with mechanisms of cell death.

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