Death by necrosis

Cells suffer necrotic death when exposed to extreme environmental conditions, adverse and excessive stimuli, or when deleterious mutations are encoded in their genetic material. Unlike apoptosis, which involves a highly regulated and elaborate network of biochemical events and cascades, necrosis has been considered generally to be a chaotic decadence process that effects the inexorable demise of cells otherwise not destined to die. This grim prospect is now slowly being overturned, mostly by exciting new findings in two simple model organisms, Caenorhabditis elegans and Drosophila melanogaster. Despite the wide spectrum of necrosis-initiating conditions, evidence is accumulating that execution of necrotic or neurodegenerative cell death may be carried out by a finite common set of mechanisms. Introduction Early pioneering studies of cell death delineated two major, morphologically distinct types: apoptosis and necrosis Necrosis, the second type of cell death, is radically different from apoptosis in almost every respect. The term derives from the Greek kernel 'necros', meaning 'dead' (with a sense of dismay), and refers to the accidental death of cells exposed to extreme environmental or genetically encoded insults Injured cells undergoing necrosis display gross morphological and ultra structural features that contrast sharply with those exhibited by cells undergoing apoptosis. Death is accompanied by extensive swelling of the cell, distension of various cellular organelles, clumping and random degradation of nuclear DNA, extensive plasma membrane endocytosis and autophagy It is striking that despite the profound impact of necrotic cell death on human health, the molecular events that transpire during cellular necrosis remain obscure. The dominant concept that has permeated the field stipulated that necrotic death is merely the chaotic breakdown of a cell under intolerable conditions, involving execution mechanisms almost as diverse as the triggers initiating cell death. However, relatively recent observations in simple model organisms such as Caenorhabditis elegans and Drosophila challenge these view