Research Highlight RIP Kinases Initiate Programmed Necrosis

Some lethal stimuli can induce either apoptosis or necrosis, depending on the cell type and/or experimental setting. Until recently, the molecular bases of this phenomenon were largely unknown. Now, two members of the receptor-interacting serine-threonine kinase (RIP) family, RIP1 and RIP3, have been demonstrated to control the switch between apoptotic and necrotic cell death. Some mechanistic details, however, remain controversial. Apoptosis and necrosis constitute two dis-tinct cell death modalities that are associ-ated with specific morphological and biochemical features. Prototypic apoptosis involves massive activation of caspases and manifests with chromatin conden-sation and reduction in cell volume, while the barrier function of plasma membranes is (at least initially) retained. In contrast, necrosis leads to early plasma membrane permeabilization, cytoplasmic swellin