Programmed cell death with a necrotic-like phenotype

Abstract

AbstractProgrammed cell death is the process by which an individual cell in a multicellular organism commits cellular ‘suicide’ to provide a long-term benefit to the organism. Thus, programmed cell death is important for physiological processes such as development, cellular homeostasis, and immunity. Importantly, in this process, the cell is not eliminated in response to random events but in response to an intricate and genetically defined set of internal cellular molecular events or ‘program’. Although the apoptotic process is generally very well understood, programmed cell death that occurs with a necrotic-like phenotype has been much less studied, and it is only within the past few years that the necrotic program has begun to be elucidated. Originally, programmed necrosis was somewhat dismissed as a nonphysiological phenomenon that occurs in vitro. Recent in vivo studies, however, suggest that regulated necrosis is an authentic classification of cell death that is important in mammalian development and other physiological processes, and programmed necrosis is now considered a significant therapeutic target in major pathological processes as well. Although the RIP1-RIP3-dependent necrosome complex is recognized as being essential for the execution of many instances of programmed necrosis, other downstream and related necrotic molecules and pathways are now being characterized. One of the current challenges is understanding how and under what conditions these pathways are linked together.