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NADPH oxidases: new players in TNF-induced necrotic cell death

Tom Vanden Berghe1, Wim Declercq, Peter Vandenabeele

  • 1Department for Molecular Biomedical Research, VIB, Technologiepark 927, B-9052, Ghent, Belgium.

Molecular Cell
|June 26, 2007
PubMed

Insights

Necrosis, a cell death pathway, involves reactive oxygen species (ROS). A novel tumor necrosis factor receptor 1 (TNFR1) complex activates the ROS-producing Nox1 NADPH oxidase, driving necrotic cell death.

Area of Science:

  • Cellular biology
  • Biochemistry
  • Immunology

Background:

  • Necrosis is a critical form of regulated cell death.
  • Reactive oxygen species (ROS) play a key role in necrosis.
  • Tumor necrosis factor receptor 1 (TNFR1) signaling is implicated in cell death pathways.

Purpose of the Study:

  • To elucidate the molecular mechanisms of TNFR1-induced necrosis.
  • To identify novel components of the necrotic signaling complex.
  • To investigate the role of ROS generation in necrosis.

Main Methods:

  • Biochemical assays to detect protein interactions.
  • Cell-based assays to measure cell death.
  • Analysis of signaling complex formation upon TNFR1 activation.

Main Results:

  • A novel necrotic signaling complex associated with TNFR1 was identified.
  • The complex formation is dependent on TRADD and RIP1.
  • Activated Nox1 NADPH oxidase within the complex generates ROS, crucial for necrosis.

Conclusions:

  • TNFR1 initiates a distinct necrotic pathway.
  • TRADD and RIP1 mediate the recruitment of Nox1.
  • ROS generation by Nox1 is a key effector mechanism in TNFR1-mediated necrosis.

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