title: The apoptosis-necrosis continuum: insights from genetically altered mice.
abstract: Apoptosis can be defined as a carefully regulated process, characterized by specific morphologic and biochemical features. It is initiated by both physiologic and pathologic stimuli, and its full expression requires a signaling cascade in which caspase activation plays a central role. Knockout mice lacking key genes encoding proteins constituting the core apoptotic cascade have helped us to establish the functional hierarchy of the mechanisms controlling apoptosis in animal development and, to a lesser extent, in disease. Induced mutant mice have also revealed the intimate crosstalk between apoptotic and other homeostatic pathways and have defined distinct temporal and tissue-specific roles of individual apoptotic effectors. Eliminating genes controlling caspase-dependent apoptosis can convert an apoptotic phenotype to a necrotic one, both in vitro and in vivo. This suggests that necrosis and apoptosis represent morphologic expressions of a shared biochemical network through both caspase-dependent mechanisms as well as non-caspase-dependent effectors such as cathepsin B and apoptosis-inducing factor. The cell death program, whether by apoptosis or necrosis, is mediated through an integrated cascade, which can be accessed at multiple sites, and propagated through numerous branch points. An understanding of the physiologic conditions that influence these decisions is required to adequately prevent, or induce, cell death.
authors.affiliation: Section of Comparative Medicine, Yale School of Medicine, 375 Congress Avenue, 126 LSOG, New Haven, CT 06520, USA. caroline.zeiss@yale.edu
authors.forename: C J
authors.initials: CJ
authors.lastname: Zeiss
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000502:physiology*; D008928:Mitochondria / Q000235:genetics / Q000502:physiology; D009336:Necrosis
chemical_list: D020169:Caspases