Physiological consequences of programmed necrosis, an alternative form of cell demise

Cell death occurs spontaneously or in response to external stimuli, and can be largely subdivided into apoptosis and necrosis by the distinct morphological and biochemical features. Unlike apoptosis, necrosis was recognized as the passive and unwanted cell demise committed in a non-regulated and disorganized manner. However, under specific conditions such as caspase intervention, necrosis has been proposed to be regulated in a well-orchestrated way as a backup mechanism of apoptosis. The term programmed necrosis has been coined to describe such an alternative cell death. Recently, at least some regulators governing programmed necrosis have been identified and demonstrated to be interconnected via a wide network of signal pathways by further extensive studies. There is growing evidence that programmed necrosis is not only associated with pathophysiological diseases, but also provides innate immune response to viral infection. Here, we will introduce recent updates on the molecular mechanism and physiological significance of programmed necrosis.