Molecular pathways of different types of cell death: Many roads to death

Abstract

Cell death is a fundamental cellular response that has a crucial role in shaping our bodies during development and in regulating tissue homeostasis by eliminating unwanted cells. Three major morphologies of cell death have been described: apoptosis (type I), cell death associated with autophagy (type II) and necrosis (type III). In mammalian cells, the apoptotic response is mediated by either an intrinsic or an extrinsic pathway, depending on the origin of the death stimuli, and is almost always caspase-dependent. For a long time necrosis has been considered to be an accidental and uncontrolled form of cell death. However, evidence is accumulating that necrotic cell death in some cases can be as well controlled and programmed as caspase-dependent apoptosis. Autophagy is foremost a survival mechanism that is activated in cells subjected to nutrient or obligate growth factor deprivation. When cellular stress continues, cell death may continue by autophagy alone, or else it often becomes associated with features of apoptotic or necrotic cell death, depending on the stimulus and cell type. It is debatable whether autophagic cell death is an alternative way of dying, different from apoptotic and necrotic cell death, or whether failure of autophagy to rescue the cell can lead to cell death by either pathway. The aim of this chapter is to provide a general overview of current knowledge on signalling events that result in apoptosis, necrosis and cell death associated with autophagy. © 2009 Springer Netherlands.