Editing Programmed cell death (section)

=== Apoptosis ===

[[Apoptosis]] is the process of programmed cell death (PCD) that may occur in [[multicellular organisms]].<ref>{{cite book|last=Green|first=Douglas|title=Means To An End|year=2011|publisher=Cold Spring Harbor Laboratory Press|location=New York|isbn=978-0-87969-888-1 |url=http://celldeathbook.wordpress.com/}}</ref> [[Biochemical]] events lead to characteristic cell changes ([[Morphology (biology)|morphology]]) and death. These changes include [[Bleb (cell biology)|blebbing]], cell shrinkage, [[Cell nucleus|nuclear]] fragmentation, [[chromatin condensation]], and [[chromosome|chromosomal]] [[DNA]] fragmentation. It is now thought that- in a developmental context- cells are induced to positively commit suicide whilst in a homeostatic context; the absence of certain survival factors may provide the impetus for suicide. There appears to be some variation in the morphology and indeed the biochemistry of these suicide pathways; some treading the path of "apoptosis", others following a more generalized pathway to deletion, but both usually being genetically and synthetically motivated. There is some evidence that certain symptoms of "apoptosis" such as endonuclease activation can be spuriously induced without engaging a genetic cascade, however, presumably true apoptosis and programmed cell death must be genetically mediated. It is also becoming clear that mitosis and apoptosis are toggled or linked in some way and that the balance achieved depends on signals received from appropriate growth or survival factors.<ref name="Apoptosis or programmed cell death?">{{cite journal|last=D. Bowen|first=Ivor|title=Cell Biology International 17|journal=Cell Biology International|volume=17|issue=4|year=1993|pages=365–380|url=http://www.cellbiolint.org/cbi/017/cbi0170365.htm#CitedBy|access-date=2012-10-03|archive-url=https://web.archive.org/web/20140312224446/http://www.cellbiolint.org/cbi/017/cbi0170365.htm#CitedBy|archive-date=2014-03-12|url-status=dead|doi=10.1006/cbir.1993.1075|pmid=8318948|s2cid=31016389|url-access=subscription}}</ref>

==== Extrinsic Vs. Intrinsic Pathways ====
There are two different potential pathways that may be followed when apoptosis is needed. There is the extrinsic pathway and the intrinsic pathway. Both pathways involve the use of caspases - crucial to cell death.{{cn|date=November 2024}}

===== Extrinsic Pathway =====
{{See also|Activation-induced cell death}}
The extrinsic pathway involves specific receptor ligand interaction. Either the FAS ligand binds to the FAS receptor or the TNF-alpha ligand can bind to the TNF receptor. In both situations there is the activation of initiator caspase. The extrinsic pathway can be activated in two ways. The first way is through fast ligan TNF-alpha binding or through a cytotoxic t-cell. The cytotoxic T-cell can attach itself to a membrane, facilitating the release of granzyme B. Granzyme B perforates the target cell membrane and in turn allows the release of perforin. Finally, perforin creates a pore in the membrane, and releases the caspases which leads to the activation of caspase 3. This initiator caspase may cause the cleaving of inactive caspase 3, causing it to become cleaved caspase 3. This is the final molecule needed to trigger cell death.<ref>{{Cite web |title= Apoptosis &#124; Intrinsic and extrinsic pathway &#124; USMLE step 1 &#124; Pathology| website=[[YouTube]] | date=8 January 2023 |url=https://www.youtube.com/watch?v=fwXpI6HdaZo.}}</ref>

===== Intrinsic Pathway =====
The intrinsic pathway is caused by cell damage such as DNA damage or UV exposure. This pathway takes place in the mitochondria and is mediated by sensors called Bcl sensors, and two proteins called BAX and BAK. These proteins are found in a majority of higher mammals as they are able to pierce the mitochondrial outer membrane - making them an integral part of mediating cell death by apoptosis. They do this by orchestrating the formation of pores within the membrane - essential to the release of cytochrome c. However, cytochrome c is only released if the mitochondrial membrane is compromised. Once cytochrome c is detected, the apoptosome complex is formed. This complex activates the executioner caspase which causes cell death. This killing of the cells may be essential as it prevents cellular overgrowth which can result in disease such as cancer. There are another two proteins worth mentioning that inhibit the release of cytochrome c in the mitochondria. Bcl-2 and Bcl-xl are anti-apoptotic and therefore prevent cell death. There is a potential mutation that can occur in that causes the overactivity of Bcl-2. It is the translocation between chromosomes 14 and 18. This over activity can result in the development of follicular lymphoma.<ref>{{Cite web |title=Apoptosis | website=[[YouTube]] | date=30 March 2019 |url=https://www.youtube.com/watch?v=jRZHDhHf3tA}}</ref>