Programmed necrosis/necroptosis: An inflammatory form of cell death

Abstract

It was not long ago when necrosis was thought to be cell injury caused by nonspecific physical trauma. In recent years, a dedicated pathway that triggers necrosis in response to TNF-like death cytokines, certain toll-like receptors, and in response to viral pathogens was described. Signaling adaptors that contain the RIP homotypic interaction motif (RHIM), such as receptor interacting protein kinase (RIPK) 1 and RIPK3, are key inducers for this form of regulated necrosis, often referred to as programmed necrosis or necroptosis. Genetic and biochemical experiments show that RIP kinase-dependent necrosis and caspase-dependent apoptosis are intimately linked. Unlike apoptosis, necrosis tends to promote inflammation. Emerging evidence indicates that the pro-inflammatory nature of necrosis is a critical driver in a wide range of disease pathologies. In this chapter, I discuss the molecular pathway that controls necrosis and how it contributes to different inflammatory diseases.