Stable Identifier
Homo sapiens
Locations in the PathwayBrowser
Click the image above or here to open this pathway in the Pathway Browser
Apoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and membrane blebbing characterize apoptosis in general. Mitochondria remain morphologically unchanged. In 1972 Kerr et al introduced the concept of apoptosis as a distinct form of "cell-death", and the mechanisms of various apoptotic pathways are still being revealed today.
The two principal pathways of apoptosis are (1) the Bcl-2 inhibitable or intrinsic pathway induced by various forms of stress like intracellular damage, developmental cues, and external stimuli and (2) the caspase 8/10 dependent or extrinsic pathway initiated by the engagement of death receptors
The caspase 8/10 dependent or extrinsic pathway is a death receptor mediated mechanism that results in the activation of caspase-8 and caspase-10. Activation of death receptors like Fas/CD95, TNFR1, and the TRAIL receptor is promoted by the TNF family of ligands including FASL (APO1L OR CD95L), TNF, LT-alpha, LT-beta, CD40L, LIGHT, RANKL, BLYS/BAFF, and APO2L/TRAIL. These ligands are released in response to microbial infection, or as part of the cellular, humoral immunity responses during the formation of lymphoid organs, activation of dendritic cells, stimulation or survival of T, B, and natural killer (NK) cells, cytotoxic response to viral infection or oncogenic transformation.
The Bcl-2 inhibitable or intrinsic pathway of apoptosis is a stress-inducible process, and acts through the activation of caspase-9 via Apaf-1 and cytochrome c. The rupture of the mitochondrial membrane, a rapid process involving some of the Bcl-2 family proteins, releases these molecules into the cytoplasm. Examples of cellular processes that may induce the intrinsic pathway in response to various damage signals include: auto reactivity in lymphocytes, cytokine deprivation, calcium flux or cellular damage by cytotoxic drugs like taxol, deprivation of nutrients like glucose and growth factors like EGF, anoikis, transactivation of target genes by tumor suppressors including p53.
In many non-immune cells, death signals initiated by the extrinsic pathway are amplified by connections to the intrinsic pathway. The connecting link appears to be the truncated BID (tBID) protein a proteolytic cleavage product mediated by caspase-8 or other enzymes.
Literature References
PubMed ID Title Journal Year
15218528 Apoptosis and disease: a life or death decision

MacFarlane, M, Williams, AC

EMBO Rep 2004
12505355 History of the events leading to the formulation of the apoptosis concept

Kerr, JF

Toxicology 2002
14561771 Ways of dying: multiple pathways to apoptosis.

Adams, JM

Genes Dev 2003
14634621 The Bcl-2 family: roles in cell survival and oncogenesis.

Adams, JM, Huang, DC, Cory, S

Oncogene 2003
4561027 Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics

Currie, AR, Kerr, JF, Wyllie, AH

Br J Cancer 1972
12209154 The Bcl2 family: regulators of the cellular life-or-death switch

Adams, JM, Cory, S

Nat Rev Cancer 2002
12189384 Targeting death and decoy receptors of the tumour-necrosis factor superfamily

Ashkenazi, A

Nat Rev Cancer 2002
Event Information
Go Biological Process
Orthologous Events
Cite Us!