REVIEW

Cell Research (2008): 343-349
© 2008 IBCB, SIBS, CAS All rights reserved 1001-0602/06 $ 30.00
www.nature.com/cr

TNFα and reactive oxygen species in necrotic cell death

Michael J Morgan, You-Sun Kim and Zheng-gang Liu

Correspondence: Zheng-gang Liu E-mail: zgliu@helix.nih.gov

Download as printable (PDF) file Full Text (html)file Search Medline for articles by: Michael J Morgan

Death receptors, including the TNF receptor-1 (TNF-RI), have been shown to be able to initiate caspase-independent cell death. This form of "necrotic cell death" appears to be dependent on the generation of reactive oxygen species. Recent data have indicated that superoxide generation is dependent on the activation of NADPH oxidases, which form a complex with the adaptor molecules RIP1 and TRADD. The mechanism of superoxide generation further establishes RIP1 as the central molecule in ROS production and cell death initiated by TNFα and other death receptors. A role for the sustained JNK activation in necrotic cell death is also suggested. The sensitization of virus-infected cells to TNFα indicates that necrotic cell death may represent an alternative cell death pathway for clearance of infected cells.

Cell Research (2008) 18:343-349. doi: 10.1038/cr.2008.31; published online 26 February 2008

Keywords: TNF, necrosis, Nox1, TRADD, RIP1, ROS, JNK