Editing Cell death (section)

=== Programmed cell death ===
{{excerpt|Programmed cell death}}
Programmed cell death (PCD) is cell death mediated by an intracellular program.<ref>
{{cite journal | vauthors = Engelberg-Kulka H, Amitai S, Kolodkin-Gal I, Hazan R | title = Bacterial programmed cell death and multicellular behavior in bacteria | journal = PLOS Genetics | volume = 2 | issue = 10 | pages = e135 | date = October 2006 | pmid = 17069462 | pmc = 1626106 | doi = 10.1371/journal.pgen.0020135 | doi-access = free }}
</ref><ref name="Green_2011">{{cite book| vauthors = Green D |title=Means To An End|year=2011|publisher=Cold Spring Harbor Laboratory Press|location=New York|isbn=978-0-87969-887-4|url=http://celldeathbook.wordpress.com/}}</ref> PCD is carried out in a regulated [[biological process|process]], which usually confers advantage during an organism's [[biological life cycle|life-cycle]]. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between  the fingers [[Apoptosis|apoptose]]; the result is that the digits separate. PCD serves fundamental functions during both plant and [[metazoa]] (multicellular animals) tissue development.

==== Apoptosis ====
[[File:Apoptotic_cell_disassembly.png|thumb|Morphological changes associated with apoptosis]]
[[Apoptosis]] is the processor of programmed cell death (PCD) that may occur in [[multicellular organisms]].<ref name="Green_2011" /> [[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?2">{{cite journal | vauthors = Bowen ID | title = Apoptosis or programmed cell death? | journal = Cell Biology International | volume = 17 | issue = 4 | pages = 365–380 | date = April 1993 | pmid = 8318948 | doi = 10.1006/cbir.1993.1075 | s2cid = 31016389 }}</ref>
[[File:Autophagy.jpg|thumb|Example events in autophagy]]
Certain key proteins primarily employed in the [[DNA repair|repair of DNA damage]] can also induce apoptosis when [[DNA damage (naturally occurring)|DNA damage]] exceeds the cell’s repair capability.<ref>{{cite journal |vauthors=Bernstein C, Bernstein H, Payne CM, Garewal H |title=DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis |journal=Mutat Res |volume=511 |issue=2 |pages=145–78 |date=June 2002 |pmid=12052432 |doi=10.1016/s1383-5742(02)00009-1 |bibcode=2002MRRMR.511..145B |url=}}</ref>   These dual role proteins protect against proliferation of unstable damaged cells that might lead to cancer.

==== Autophagy ====
Autophagy is ''[[cytoplasm]]ic'', characterized by the formation of large [[vacuole]]s that eat away [[organelle]]s in a specific sequence prior to the destruction of the [[cell nucleus|nucleus]].<ref>
{{cite journal | vauthors = Schwartz LM, Smith SW, Jones ME, Osborne BA | title = Do all programmed cell deaths occur via apoptosis? | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 3 | pages = 980–984 | date = February 1993 | pmid = 8430112 | pmc = 45794 | doi = 10.1073/pnas.90.3.980 | doi-access = free | bibcode = 1993PNAS...90..980S }};and, for a more recent view, see {{cite journal | vauthors = Bursch W, Ellinger A, Gerner C, Fröhwein U, Schulte-Hermann R | title = Programmed cell death (PCD). Apoptosis, autophagic PCD, or others? | journal = Annals of the New York Academy of Sciences | volume = 926 | issue = 1 | pages = 1–12 | year = 2000 | pmid = 11193023 | doi = 10.1111/j.1749-6632.2000.tb05594.x | s2cid = 27315958 | bibcode = 2000NYASA.926....1B }}</ref> [[Macroautophagy]], often referred to as [[autophagy]], is a [[catabolic]] process that results in the [[Autophagosome|autophagosomic]]-[[Lysosome|lysosomal]] degradation of bulk [[cytoplasm]]ic contents, abnormal protein aggregates, and excess or damaged [[organelle]]s. Autophagy is generally activated by conditions of [[nutrient]] deprivation but has also been associated with [[Physiology|physiolog]]ical as well as [[Pathology|patholog]]ical processes such as development, differentiation, [[neurodegenerative]] [[disease]]s, [[stress (physiology)|stress]], [[infection]] and [[cancer]].

==== Other variations of PCD ====
Other pathways of programmed cell death have been discovered.<ref>
{{cite journal | vauthors = Kroemer G, Martin SJ | title = Caspase-independent cell death | journal = Nature Medicine | volume = 11 | issue = 7 | pages = 725–730 | date = July 2005 | pmid = 16015365 | doi = 10.1038/nm1263 | s2cid = 8264709 }}</ref> Called "non-apoptotic programmed cell-death" (or "[[caspase]]-independent programmed cell-death"), these alternative routes to death are as efficient as apoptosis and can function as either backup mechanisms or the main type of PCD.

Some such forms of programmed cell death are [[anoikis]], almost identical to apoptosis except in its induction; [[cornification]], a form of cell death exclusive to the eyes; [[excitotoxicity]]; [[ferroptosis]], an iron-dependent form of cell death<ref>{{cite journal | vauthors = Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B, Stockwell BR | title = Ferroptosis: an iron-dependent form of nonapoptotic cell death | journal = Cell | volume = 149 | issue = 5 | pages = 1060–1072 | date = May 2012 | pmid = 22632970 | pmc = 3367386 | doi = 10.1016/j.cell.2012.03.042 }}</ref> and [[Wallerian degeneration]].

Plant cells undergo particular processes of PCD similar to autophagic cell death. However, some common features of PCD are highly conserved in both plants and metazoa.

[[Activation-induced cell death (AICD)]] is a programmed cell death caused by the interaction of Fas receptor (Fas, CD95)and Fas ligand (FasL, CD95 ligand).<ref name="Zhang">{{cite journal | vauthors = Zhang J, Xu X, Liu Y | title = Activation-induced cell death in T cells and autoimmunity | journal = Cellular & Molecular Immunology | volume = 1 | issue = 3 | pages = 186–92 | date = June 2004 | pmid = 16219166 | doi = }}</ref> It occurs as a result of repeated stimulation of specific T-cell receptors (TCR) and it helps to maintain the periphery immune tolerance.<ref name="pmid9159213">{{cite journal | vauthors = Kabelitz D, Janssen O | title = Antigen-induced death of T-lymphocytes | journal = Frontiers in Bioscience: A Journal and Virtual Library | volume = 2 | issue = 4| pages = d61–77 | date = February 1997 | pmid = 9159213 | doi = 10.2741/a175 }}</ref>  Therefore, an alteration of the process may lead to autoimmune diseases.<ref name="Zhang" /> In the other words AICD is the negative regulator of activated T-lymphocytes.

[[Ischemic cell death]], or oncosis, is a form of accidental, or passive cell death that is often considered a lethal injury. The process is characterized by [[mitochondria]]l [[swelling (medical)|swelling]], [[cytoplasm]] [[vacuolization]], and swelling of the [[Cell nucleus|nucleus]] and cytoplasm.<ref>{{cite encyclopedia|title=Oncosis|url=http://www.copewithcytokines.de/cope.cgi?key=Oncosis|access-date=10 August 2010 | encyclopedia = Cell Communication Online Pathfinder Encyclopaedia (COPE) }}</ref>

[[Mitotic catastrophe]] is an oncosuppressive mechanism that can lead to cell death that is due to premature or inappropriate entry of cells into mitosis.<ref>{{cite journal | vauthors = Vitale I, Galluzzi L, Castedo M, Kroemer G | title = Mitotic catastrophe: a mechanism for avoiding genomic instability | journal = Nature Reviews. Molecular Cell Biology | volume = 12 | issue = 6 | pages = 385–392 | date = June 2011 | pmid = 21527953 | doi = 10.1038/nrm3115 | s2cid = 22483746 }}</ref>  It is the most common mode of cell death in cancer cells exposed to [[ionizing radiation]] and many other anti-cancer treatments.<ref>{{cite book| chapter-url=http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-93322008000100021| chapter = Mitotic Catastrophe in Apoptosis, Senescence, and Cancer| vauthors = Ianzini F, Mackey MA | title = Revista Brasileira de Ciências Farmacêuticas | veditors = Gewirtz DA, Holt SE, Grant S |date=2007|volume=44 |publisher=Humana Press|isbn=978-1-58829-527-9|pages=73–91|doi=10.1007/978-1-59745-221-2}}</ref>

[[Immunogenic cell death]] or immunogenic [[apoptosis]] is a form of cell death caused by some cytostatic agents such as [[anthracyclines]], oxaliplatin and bortezomib, or [[radiotherapy]] and [[photodynamic therapy]] (PDT).<ref name="pmid19720113">{{cite journal | vauthors = Garg AD, Nowis D, Golab J, Vandenabeele P, Krysko DV, Agostinis P | title = Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation | journal = Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | volume = 1805 | issue = 1 | pages = 53–71 | date = January 2010 | pmid = 19720113 | doi = 10.1016/j.bbcan.2009.08.003 | url = https://lirias.kuleuven.be/bitstream/123456789/632508/2/BBA-RC%20Review%20-%20Final%20Revised%20MS.doc | url-access = subscription }}</ref>

[[Pyroptosis]] is a highly inflammatory form of programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response in myeloid cells.<ref name="Darzynkiewicz_1997">{{cite journal | vauthors = Darzynkiewicz Z, Juan G, Li X, Gorczyca W, Murakami T, Traganos F | title = Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis) | journal = Cytometry | volume = 27 | issue = 1 | pages = 1–20 | date = January 1997 | pmid = 9000580 | doi = 10.1002/(sici)1097-0320(19970101)27:1<1::aid-cyto2>3.0.co;2-l | doi-access = free }}</ref>

[[PANoptosis]] is an innate immune, lytic cell death pathway initiated by innate immune sensors and driven by caspases and RIP kinases through PANoptosome complexes. To date, several PANoptosome complexes have been characterized, including ZBP1-, AIM2-, RIPK1-, NLRC5-/NLRP12-, and NLRP3-PANoptosomes. PANoptosis is critical in innate immune responses for host defense, but it has also been implicated in inflammation and pathology in inflammatory diseases, infections, and cancers. <ref name=":10">{{Cite web |title=St. Jude finds NLRP12 as a new drug target for infection, inflammation and hemolytic diseases |url=https://www.stjude.org/media-resources/news-releases/2023-medicine-science-news/st-jude-finds-nlrp12-as-a-new-drug-target.html |access-date=2024-03-07 |website=www.stjude.org |language=en}}</ref><ref name=":12">{{Cite journal |last1=Zheng |first1=Min |last2=Karki |first2=Rajendra |last3=Vogel |first3=Peter |last4=Kanneganti |first4=Thirumala-Devi |date=2020-04-30 |title=Caspase-6 Is a Key Regulator of Innate Immunity, Inflammasome Activation, and Host Defense |journal=Cell |volume=181 |issue=3 |pages=674–687.e13 |doi=10.1016/j.cell.2020.03.040 |issn=1097-4172 |pmc=7425208 |pmid=32298652}}</ref><ref>{{Cite journal |last1=Christgen |first1=Shelbi |last2=Zheng |first2=Min |last3=Kesavardhana |first3=Sannula |last4=Karki |first4=Rajendra |last5=Malireddi |first5=R. 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K. Subbarao |last2=Kesavardhana |first2=Sannula |last3=Karki |first3=Rajendra |last4=Kancharana |first4=Balabhaskararao |last5=Burton |first5=Amanda R. |last6=Kanneganti |first6=Thirumala-Devi |date=2020-12-11 |title=RIPK1 Distinctly Regulates Yersinia-Induced Inflammatory Cell Death, PANoptosis |journal=ImmunoHorizons |volume=4 |issue=12 |pages=789–796 |doi=10.4049/immunohorizons.2000097 |issn=2573-7732 |pmc=7906112 |pmid=33310881}}</ref><ref name=":14">{{Cite journal |last1=Sundaram |first1=Balamurugan |last2=Pandian |first2=Nagakannan |last3=Mall |first3=Raghvendra |last4=Wang |first4=Yaqiu |last5=Sarkar |first5=Roman |last6=Kim |first6=Hee Jin |last7=Malireddi |first7=R. K. 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[[Phagoptosis]] is cell death resulting from a live cell being phagocytosed (i.e. eaten) by another cell (usually a phagocyte), resulting in death and digestion of the engulfed cell. Phagoptosis can occur to cells that are pathogenic, cancerous, aged, damaged or excess to requirements.<ref>{{cite journal | vauthors = Brown GC | title = Cell death by phagocytosis | journal = Nature Reviews. Immunology | volume = 24 | issue = 2 | pages = 91–102 | date = February 2024 | pmid = 37604896 | doi = 10.1038/s41577-023-00921-6 }}</ref>