Die another way--non-apoptotic mechanisms of cell death.
Regulated, programmed cell death is crucial for all multicellular organisms. Cell death is essential in many processes, including tissue sculpting during embryogenesis, development of the immune system and destruction of damaged cells. The best-studied form of programmed cell death is apoptosis, a process that requires activation of caspase proteases. Recently it has been appreciated that various non-apoptotic forms of cell death also exist, such as necroptosis and pyroptosis. These non-apoptotic cell death modalities can be either triggered independently of apoptosis or are engaged should apoptosis fail to execute. In this Commentary, we discuss several regulated non-apoptotic forms of cell death including necroptosis, autophagic cell death, pyroptosis and caspase-independent cell death. We outline what we know about their mechanism, potential roles in vivo and define outstanding questions. Finally, we review data arguing that the means by which a cell dies actually matters, focusing our discussion on inflammatory aspects of cell death.
Cancer Research UK Beatson Institute, Institute of Cancer Sciences, University of Glasgow, Switchback Road, Glasgow G61 1BD, UK stephen.tait@glasgow.ac.uk douglas.green@stjude.org.
Stephen W G
SW
Tait
Cancer Research UK Beatson Institute, Institute of Cancer Sciences, University of Glasgow, Switchback Road, Glasgow G61 1BD, UK.
Gabriel
G
Ichim
Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA stephen.tait@glasgow.ac.uk douglas.green@stjude.org.
Douglas R
DR
Green
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D006801:Humans
MLKL; Mitochondria; Necroptosis; Pyroptosis; RIPK3