Programmed cell death
Cell death from internal events, crucial for development and homeostasis.
Programmed cell death (PCD), also called cell suicide or cellular suicide, is the death of a cell resulting from internal events such as apoptosis or autophagy. It is a biological process that typically confers an advantage during an organism's lifecycle, for example in the separation of fingers and toes during human embryonic development. PCD serves fundamental functions in both plant and animal tissue development. The concept of programmed cell death was first introduced in 1964 in relation to insect tissue development, predating the term "apoptosis" by about eight years. The term PCD has caused some confusion, leading to efforts to clarify it through mechanistic and evolutionary definitions. Early mechanistic insight came from studying the BCL2 gene, which was found to promote cancer not by stimulating cell proliferation but by preventing lymphoma cells from undergoing self-destruction. PCD research gained significant recognition with the 2002 Nobel Prize in Physiology or Medicine awarded to Sydney Brenner, H. Robert Horvitz, and John E. Sulston. Apoptosis and autophagy are both forms of PCD, while necrosis, long considered a non-physiological process caused by external factors like trauma or infection, was later found to include a programmed form called necroptosis. Necroptosis is thought to serve as a backup cell-death pathway when apoptosis signaling is blocked by factors such as viruses or mutations. Other types of regulated necrosis have since been discovered, sharing signaling events with both necroptosis and apoptosis. Apoptosis itself involves characteristic morphological changes including cell shrinkage, nuclear fragmentation, and DNA fragmentation, and can be triggered through either an extrinsic pathway involving receptor-ligand interactions or an intrinsic pathway mediated by mitochondrial damage and proteins such as BAX and BAK.
- field
- Cell biology
- known_for
- Concept of programmed cell death, including apoptosis, autophagy, and necroptosis
- types
- Apoptosis (Type I), Autophagic cell death (Type II), Necroptosis
Lore & Background
Programmed cell death (PCD) is a genetically controlled process in which a cell actively destroys itself, often conferring an advantage during an organism's lifecycle. It is fundamental to tissue development in both plants and animals; for instance, the separation of fingers and toes in a human embryo occurs because cells between the digits undergo apoptosis. PCD encompasses several distinct forms. Apoptosis, or Type I cell death, involves characteristic morphological changes including cell shrinkage, membrane blebbing, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation. Autophagic cell death, or Type II, is marked by the formation of large vacuoles that sequentially consume organelles before the nucleus is destroyed. Both apoptosis and autophagy are genetically mediated. A third form, necroptosis, is a programmed version of necrosis—traditionally seen as a non-physiological response to injury or infection—and can serve as a backup when apoptosis signaling is blocked by viruses or mutations. Other regulated necrosis types have also been identified. Apoptosis proceeds via two pathways: the extrinsic pathway, triggered by receptor-ligand interactions such as FAS or TNF-alpha binding, which activates initiator caspases; and the intrinsic pathway, initiated by cell damage like DNA damage or UV exposure, which occurs in the mitochondria. The intrinsic pathway relies on BCL sensor proteins and the BAX and BAK proteins, which pierce the mitochondrial membrane to release cytochrome c, forming the apoptosome complex that activates executioner caspases. The term "programmed cell death" was first used in 1964 by Lockshin and Williams in relation to insect development, predating the term "apoptosis" by about eight years. Early mechanistic insight came from studying the BCL2 gene, which promotes cancer not by stimulating proliferation but by preventing lymphoma cells from undergoing suicide.
Reader's Guide
Robert Horvitz, and John E. Sulston. The field encompasses multiple pathways: apoptosis (Type I), autophagic cell death (Type II), and necroptosis, a form of programmed necrosis recognized in the 2000s. Necroptosis can serve as a backup to apoptosis when apoptosis signaling is blocked by viruses or mutations. Other regulated necrosis forms have since been discovered, sharing signaling events with necroptosis and apoptosis. The balance between mitosis and apoptosis depends on signals from growth or survival factors. Autophagy and apoptosis are connected both positively and negatively, with extensive crosstalk; for example, Bcl-2 inhibits Beclin-1-dependent autophagy, functioning as both a pro-survival and anti-autophagic regulator.
Did You Know?
- BCL2, an oncogene in follicular lymphoma, promotes cancer by stopping lymphoma cells from killing themselves.
- Necroptosis was recognized in the 2000s as a programmed form of necrosis that can serve as a backup to apoptosis.
- Autophagy is generally activated by nutrient deprivation but is also associated with development, differentiation, neurodegenerative diseases, stress, infection, and cancer.
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