Editors' ChoiceCell Biology

The Grim RIPper

Science Signaling  21 Jul 2009:
Vol. 2, Issue 80, pp. ec246
DOI: 10.1126/scisignal.280ec246

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), Zhang et al. 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 (ROS) was necessary for TNF-induced necrosis, and depletion of RIP3 reduced the generation of ROS. Thus, RIP3 may participate in the mechanisms that link energy metabolism with mechanisms of cell death.

D.-W. Zhang, J. Shao, J. Lin, N. Zhang, B.-J. Lu, S.-C. Lin, M.-Q. Dong, J. Han, RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325, 332–336 (2009). [Abstract] [Full Text]