Regulation of the apoptosis–necrosis switch

Execution of the apoptotic program involves a relatively limited number of pathways. According to a general view, these would converge to activate the caspase family of proteases. However, there is increasing evidence that apoptotic-like features can also be found when caspases are inhibited. Moreover, under pathological conditions, apoptosis and nonapoptotic death paradigms are often interwined, which suggest that, in vivo, cells may use diverging execution pathways. Molecular switches between apoptosis and necrosis include adenosine triphosphate-dependent steps in the activation of caspases or steps sensitive to reactive oxygen/nitrogen species. In turn, caspase activation can cause necrosis by promoting ion overload.