necrotic cell death

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I wonder why 'necrotic cell death' is not a GO term. It seems that it should be a sibling of apoptosis. http://www.ucihs.uci.edu/anatomy/histo/Old\_Files\_2005/corenotes/celldeath2004.pdf

Necrotic cell death was found in the protist Dictyostelium. From PMID 17150370:

" ...developmental stimuli ... led in an autophagy mutant to a stereotyped sequence of events characteristic of necrotic cell death [37]. This sequence included swift mitochondrial uncoupling with mitochondrial dichlorofluorescein-diacetate fluorescence, ATP depletion and increased oxygen consumption. This was followed by perinuclear clustering of dilated mitochondria (Figs. 4e and 5d). Rapid plasma membrane rupture then occurred.

I don't know much about this, so any insights into cell death are appreciated.

Thanks, Petra

Reported by: pfey

Original Ticket: "geneontology/ontology-requests/4268":https://sourceforge.net/p/geneontology/ontology-requests/4268

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I know that there are types of necrotic cell death that are "programmed." There was a nice review of cell death beyond apoptosis a year or two ago -- I'll look for it tomorrow when I am back at work.

-- Alex

Original comment by: addiehl

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Dear Alex and Petra,

I was just myself wondering whether there should be a child term to GO:0012501 - programmed cell death that would be "hypersensitive cell death" (instead of "hypersensitive response", the term there now, which is defined as strictly a plant term. Would this term (hypersensivie cell death) be a term that would work instead of "necrotic cell death", and could it serve both plant and animal communities? I'm envisioning that if we could have that term, then the "hypersensitive response" term could be obsoleted (because the HR includes not only programmed cell death [necrotic usually] but also other types of defense defense responses. HR could then be made a broad synonym to "hypersensitive cell death."

Candace

Original comment by: ccollmer

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Petra and Candace,

The review is PMID:15784530, Fink SL, Cookson BT. "Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells." Infect Immun. 2005 Apr;73(4):1907-16. (http://iai.asm.org/cgi/content/full/73/4/1907?view=long&pmid=15784530)

I think we should add a necrosis term of some type, and look forward to any ideas you have.

-- Alex

Original comment by: addiehl

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Hi Alex and Petra,

Thanks for the article, Alex -- I'll read through it and send my thoughts as soon as possible.

Candace

Original comment by: ccollmer

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Hi Alex, Candace, thanks for the review and the discussion. For now I made the annotation with GO:0016244, non-apoptotic programmed cell death (Cell death resulting from activation of endogenous cellular processes, by a mechanism other than apoptosis.). I'm not happy with that term as the def or even the term is too general. I'll also send my ideas asap.

Petra

Original comment by: pfey

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Ok, I read over the review, and here's what I learned: These authors clearly think that 'necrosis' per se just "describes the postmortem observation of dead cells that have come to equilibrium with their environment." In that sense, GO is probably ok with having 'necrosis' as a related synonym for many cell death terms. The authors aim to end the distinction of necrotic and apoptotic cell death, as they see necrosis as the end stage. They also think that it's all 'programmed', which they define as "the fixed pathway followed by dying cells, regardless of the mechanism". Though with oncosis they are most vague if it's programmed, and say "Furthermore, increasing genetic data indicate that oncosis requires an intrinsic molecular program". In that sense, coming up with the correct structure for GO needs maybe a bit more reading. The figure and the table in the review give a nice overview.

Regarding the term I'm looking for, I think the authors call this 'oncosis' ("the prelethal process that occurs in ATP-depleted cells that manifest the morphological changes of swelling and eventual membrane permeability"). This describes pretty well what authors in my paper call "necrotic cell death". I'm just not sure yet that this term can really go under 'programmed cell death', though the authors of the review clearly lean that way.

Candace, I don't know how 'hypersensitive cell death' fits into this. What I got from the review is just the clear distinction between apoptotic and autophagic cell death which is non-inflammatory, and oncosis and especially the caspase I-mediated pyroptosis being inflammatory.

So much for today, Petra

Original comment by: pfey

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Having read the review as well, I agree with Petra that the term she needs is "Oncosis". Fig 2 depicts the different types of PCD in a very nice way with the end result for all of them being necrosis or cell death. With regards to the HR in plants, I do think it is also very different from all the others described in the review (Apoptosis, Autophagy, Oncosis, Pyroptosis) in terms of the pre-lethal processes ultimately leading to cell death. HR may share some features with apoptosis and autophagy but other characteristics are unique enough for it to be kept as a different term.

Trudy

Original comment by: trutot

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I generally agree with Petra and Trudy that from reading this review, it seems like the term “oncosis” describes the type of PCD she is trying to annotate, and thus it seems that this term is a useful one to add to GO under “programmed cell death.” Its definition should capture its inflammatory nature and one of its narrow synonyms could be necrosis.

But this review also suggests that some modification of the PCD tree in GO is in order. One problem I had noticed earlier is that one child term of PCD in GO is “autophagic cell death,” a term we would agree belongs there. We see in this mini review, as well as in PMID: 11193023, that autophagy is equated with “type II programmed cell death.” However, GO currently has another GO term, a sibling to both apoptosis and autophagic cell death, which is “non-apoptotic programmed cell death.” One of the exact synonyms for this term is “type II PCD.” So, there seem to be 2 terms for the same thing.

From our reading, it seems that if we wish to keep the term “non-apoptotic PCD” in GO -- which may be a practical necessity for annotating, as the careful studies described in the mini review that allow distinguishing autophagy from oncosis from pyroptosis are not always done – then perhaps that should be a sibling term to apoptosis (as it is now), but the terms autophagic cell death, oncosis, and perhaps pyroptosis should be made children of "non-apoptotic cell death." We should also correct the defs and synonyms for all of these so that it is clear that pyroptosis and oncosis are inflammatory-promoting, and apoptosis and autophagy are not. Finally, it appears that a narrow synonym of “necrosis” would apply to apoptosis, oncosis, and pyoptosis, but not autophagy. Do others agree that these are valid conclusions from this reading?

Finally, I am still working on how to best fit in the “hypersensitive response” term here. It seems we need an additional term that would be a sibling to apoptosis = “host programmed cell death induced by symbiont,” which was proposed by Marcus earlier in a PAMGO discussion. Definition = “Cell death in a host resulting from activation of host endogenous cellular processes after direct or indirect interaction with a symbiont (defined as the smaller of two, or more, organisms engaged in symbiosis, a close interaction encompassing mutualism through parasitism). An example of direct interaction is contact with penetrating hyphae of a fungus; an example of indirect interaction is encountering symbiont-secreted molecules. COMMENT: This GO term is to be used to annotate gene products in the host, not the symbiont. For the corresponding term to use for annotating gene products in the symbiont that induce PCD in the host, see GO: 0052044 - induction by symbiont of host PCD.” This would allow the annotating of genes in a host that are activated by a pathogen attack, or by the sensing of a non-pathogenic microbe. Then, children of that term could evetually include the plant-specific, defense-specific HR (which is actually a response broader than merely induced cell death, so I’m working on how to correct that problem while also keep the term that is useful to plant pathologists. More on that will follow soon…..

But, do others agree with my summary of what to do with apoptosis, non-apoptotic PCD, autophagic cell death, oncosis, and pyroptosis? If so, I could work on writing up defs and a proposal to add the 2 new ones to GO, as children of GO term “non-apoptotic PCD” (where apparently GO term “autophagic cell death” also belongs). Or, if someone else wants to do that, that's of course fine also!

Candace

Original comment by: ccollmer

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Hi all,

Here is my proposal for what I think needs to be done to add the terms we have been talking about, to modify to make more precise the terms that are currently there, and to correct the PCD tree. I have just read Midori's opinion that GO:0016244 should be obsoleted -- I have commented on that below. Please look over this proposal carefully and send any suggested changes.

Proposal to Sourceforge item 1745083, July 4, 2007:

Proposal to add three new terms and to slightly modify four terms that currently exist; also, slightly rearrange the “programmed cell death” tree to the following:

----programmed cell death ----apoptosis ----non-apoptotic programmed cell death ----autophagic cell death ----oncosis (new term) ----pyroptosis (new term) ---- host programmed cell death induced by symbiont (new term) ----"plant" hypersensitive response (quotes indicate added word)

1) New term – “Oncosis” Definition: a proinflammatory pathway leading to cell death accompanied by cellular and organelle swelling and increased membrane permeability [source:GOC:cwc, PMID:15784530]

2) New term – “Pyroptosis” Definition: a caspase-1-dependent programmed cell death that includes membrane breakdown and proinflammatory cytokine processing [source:GOC:cwc, PMID:15784530]

3) New term – “Host programmed cell death induced by symbiont” Definition = “Cell death in a host resulting from activation of host endogenous cellular processes after direct or indirect interaction with a symbiont (defined as the smaller of two, or more, organisms engaged in symbiosis, a close interaction encompassing mutualism through parasitism). An example of direct interaction is contact with penetrating hyphae of a fungus; an example of indirect interaction is encountering symbiont-secreted molecules. COMMENT: This GO term is to be used to annotate gene products in the host, not the symbiont. For the corresponding term to use for annotating gene products in the symbiont that induce PCD in the host, see GO: 0052044 - induction by symbiont of host PCD.”

4) Modify the GO term “GO:0009626 – hypersensitive response.”
Keep the same GO id, but modify term name to “plant" [added word] hypersensitive response because its current definition says it occurs in plants. (Or, possibly, “programmed cell death via plant hypersensitive response,” as suggested by Jane Lomax on the PAMGO wiki – what do others think?) [All gene products currently annotated to HR – all Arabidopsis genes – would remain – it’s the same thing, just more explicit term name to match the current definition.] Definition (modify by a one-word addition to the original]: the rapid, "localized" [added word] death of plant cells in response to invasion by a pathogen. Add the following: “COMMENT: This GO term is to be used to annotate gene products in the plant. For the corresponding term to annotate gene products in the symbiont that induce HR in the plant, see “GO: xxxxxxx – modulation by symbiont of host defense-related programmed cell death.” [new term – to be proposed under other Sourceforge item]” Add synonyms - exact: HR; HR-PCD

5) GO:0006915 – apoptosis – add one word to the current definition: a "non-inflammatory" [added word] form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases, whose actions dismantle the cell and result in cell death. Apoptosis begins internally with condensation and subsequent fragmentation of the cell nucleus (blebbing) while the plasma membrane remains intact. Other characteristics of apoptosis include DNA fragmentation and the exposure of phosphatidyl serine on the cell surface. [source: GOC:go_curators, ISBN:0198506732] Add the following “COMMENT: “This GO term should be used to annotate genes in the organism undergoing the PCD. For annotating genes in another organism whose products modulate PCD in a host organism, see “GO: 0052040 - modulation by symbiont of host PCD.””

6) GO:0048102 – autophagic cell death – add two words to the current definition: "a non-inflammatory" [added words] destruction of a cell by its own lysosomal contents. This type of programmed cell death is seen when entire tissues, or parts thereof, are committed to destruction, and occurs by the formation of multiple acidic autophagic vacuoles within the doomed cells. [source: GOC:jic, PMID:11494315] Add synonym: “exact: type II programmed cell death” and “exact: type II cell death” [source: PMID:15784530]

7) GO:0016244 – non-apoptotic programmed cell death Midori has suggested that this term is not ontologically desirable and should be obsoleted. I have no problem with that, although it is currently useful – as described in PMID:15784530, sometimes one can tell that a type of PCD is not apoptotic but not what specific type it is; in addition, the authors expect more different types of PCD to be described eventually. That much information (PCD but not apoptotic) is actually useful. And, there are currently 24 annotations to it. If the term is kept, then Remove synonym: “exact: type II programmed cell death”

8) GO:0012501 – programmed cell death Add the following “COMMENT: This GO term should be used to annotate genes in the organism undergoing the PCD. For annotating genes in another organism whose products modulate PCD in a host organism, see “GO: 0052040 - modulation by symbiont of host PCD.”

Original comment by: ccollmer

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July 4, 2007

Sorry -- I forgot one part of what I meant to put in the proposal I sent earlier in the day -- and it's the part that started the whole Sourceforge item!

We should add the terms "necrotic cell death", and "necrosis" as narrow synonyms, I believe, to the GO terms "oncosis", "pyroptosis", and "apoptosis," but not "autophagic cell death" according to PMID:15784530.

Original comment by: ccollmer

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I think the best solution for GO:0016244 – non-apoptotic programmed cell death is to merge it with its parent, programmed cell death. This eliminates the term but preserves the annotations in an ontologically correct manner. Interested parties may go back and reannotate to one of the new terms if they choose.

I happy with the suggested terms, but am a little concerned about solely following the guide of PMID:15784530 without consulting at least one other review. It's not that I don't trust this review, but it is one viewpoint, and there may be others, given that this is an important field. Most importantly, I am concerned that we are define apoptosis as (always) non-inflammatory -- this is no doubt true in developmental and homeostatic situations, but may not necessarily be the case in situations when the apoptosis is induced by pathogens. Apoptosis in response to and induced by, for instance, viral infection is quite common. PMID:16469051, a review article about influenza infection, cites articles that alternately state that influenza induced apoptosis functions to increase T cell responses, a proinflammatory function, or that apoptosis of virally infected cells limit the release of proinflammatory cytokines. Both may be true depending on the model system. Of course, saying apoptosis is always non-inflammatory or promotes regulatory or tolerogenic processes is very neat, but I wonder if the biology is more complex.

-- Alex

Original comment by: addiehl

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In response to Alex's concern, I agree that adding the word "inflammatory" to the definition of apoptosis is actually NOT a good idea. In fact, I was about to write to Sourceforge on that very issue, having noticed that even the figure in PMID:15784530 shows that there are cases of apoptosis that can be inflammatory (just as there are some, but not all, that can induce necrosis). So, let's cancel that part of Item #5 in my proposal, and keep the definition as is, but keep the suggestion there to add a COMMENT following the def of apoptosis.

I have another question that I was also going to send re:apoptosis. I just suggested on Sourceforge that we add the narrow synonyms "necrosis" and "necrotic cell death" for the GO term apoptosis. I'm thinking now that it would be better to use "apoptotic necrosis" rather than simply "necrosis" -- do others agree?

In terms of looking at other reviews, I did do that for the term "pyroptosis" to see if others were using it, and using it in the same way in the literature. A search of PubMed turned up only 3 other articles by different authors (from the ones who wrote the review we all read), but those seemed consistent, so I decided it was worthwhile adding the term to GO.

Original comment by: ccollmer

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I like "apoptotic necrosis" as a synonym to apoptosis. A lot of early papers looking at cell death misidentify apoptosis as "necrosis" so it is good to have "necrosis" as a synonym to apoptosis in some form.

Candace, are there any other reviews or papers you would like to add as references for any of the terms?

-- Alex

Original comment by: addiehl

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Alex - I've been reading several reviews that are useful -- two in particular about apopotosis and autophagy in general, or autophagy as an important part of the HR in plants. In terms of the new terms pyroptosis and oncosis - the best review seems to be the one we all read (and cited with the definitions for those terms).

Is there a particlular term or terms that you have in mind, that you feel would benefit from more references?

Candace

Original comment by: ccollmer

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It's just that for novel terms like oncosis or pyroptosis it might be good to provide several references so that users and future developers of the GO can get a deeper understanding of these terms and be assured they are not just the creation of one set of authers.

- Alex

Original comment by: addiehl

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For oncosis, we could add this reference PMID: 15792367, which talks about apoptosis versus oncosis and 'necrosis'. So it seems they have it half-way in comparison to the review we read first. But for oncosis, they seem to be consistent with the other review. Petra

Original comment by: pfey

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I'll keeep looking for another useful review article covering pyroptosis. At the moment, the only other things I've read about that are research articles rather than reviews.

Candace

Original comment by: ccollmer

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Even research articles are acceptable if they clarify the origin or meaning of a term.

-- Alex

Original comment by: addiehl

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7/19/07:

Hi all,

Here’s a revised proposal that I think accommodates everyone’s suggestions and also adds 2 PMID references for proposed term “pyroptosis.”

Please take a look, and see if this meets everyone’s needs.

Candace

Proposal: to add three new terms and to modify four terms that currently exist; also, slightly rearrange the “programmed cell death” tree to the following:

----programmed cell death ----apoptosis ----non-apoptotic programmed cell death (most likely should be obsoleted) ----autophagic cell death (would become sibling to “apoptosis” etc.) ----oncosis (new term) (would become sibling to “apoptosis” etc.) ----pyroptosis (new term) (would become sibling to “apoptosis” etc.) ---- host programmed cell death induced by symbiont (new term) ---- hypersensitive response-related death in plants (modified term)

1) New term – “Oncosis” Definition: “a proinflammatory pathway leading to cell death accompanied by cellular and organelle swelling and increased membrane permeability [source:GOC:cwc, PMID:15784530; PMID:1579367]”

Add narrow synonyms: “necrotic cell death” and “necrosis”

If the GO term “non-apoptotic programmed cell death” is merged with its parent, “programmed cell death” (PCD) (see below), then this new term would be made a child of PCD and a sibling to GO term “apoptosis”

2) New term – “Pyroptosis” Definition: “a cell death pathway resulting from caspase-1 activity leading to plasma membrane breakdown and proinflammatory cytokine release [source:GOC:cwc, PMID:15784530; PMID:17599095; PMID:11303500]”

Add narrow synonyms: “necrotic cell death” and “necrosis”

If the GO term “non-apoptotic programmed cell death” is merged with its parent, “programmed cell death” (PCD) (see below), then this new term would be made a child of PCD and a sibling to GO term “apoptosis”

(another possible, alternative definition: a caspase-1-dependent programmed cell death that includes membrane breakdown and proinflammatory cytokine processing) [source as above]

3) New term – “Host programmed cell death induced by symbiont” Definition = “Cell death in a host resulting from activation of host endogenous cellular processes after direct or indirect interaction with a symbiont (defined as the smaller of two, or more, organisms engaged in symbiosis, a close interaction encompassing mutualism through parasitism). An example of direct interaction is contact with penetrating hyphae of a fungus; an example of indirect interaction is encountering symbiont-secreted molecules. COMMENT: This GO term is to be used to annotate gene products in the host, not the symbiont. For the corresponding term to use for annotating gene products in the symbiont that induce PCD in the host, see GO: 0052044 - induction by symbiont of host PCD.”

4) Modify the GO term “GO:0009626 – hypersensitive response.”
Keep the same GO id, but modify term name to “hypersensitive response-related death in plants” [All gene products currently annotated to HR – all Arabidopsis genes – would remain – it’s the same thing, just more explicit term name to match the current definition.] Definition (modify by a one-word addition to the original plus a new phrase following semi-colon]: “the rapid, localized death of plant cells in response to invasion by another organism, often a microbe; normally accompanied by the induction of local and systemic defense responses”

Add the following: “COMMENT: This GO term is to be used to annotate gene products in the plant. For the corresponding term to annotate gene products in the symbiont that induce HR in the plant, see “GO: xxxxxxx – modulation by symbiont of host defense-related programmed cell death.” [new term – to be proposed under other Sourceforge item]” Add synonym - exact: HR-PCD synonyms – broad: hypersensitive response; HR

5) GO:0006915 – apoptosis Add the following “COMMENT: “This GO term should be used to annotate genes in the organism undergoing the PCD. For annotating genes in another organism whose products modulate PCD in a host organism, see “GO: 0052040 - modulation by symbiont of host PCD.”” Add narrow synonyms: “necrotic cell death” and “apoptotic necrosis”

6) GO:0048102 – autophagic cell death – add one word to the current definition: a non-inflammatory destruction of a cell by its own lysosomal contents. This type of programmed cell death is seen when entire tissues, or parts thereof, are committed to destruction, and occurs by the formation of multiple acidic autophagic vacuoles within the doomed cells. [source: GOC:jic, PMID:11494315] Add synonym: “exact: type II programmed cell death” and “exact: type II cell death” [source: PMID:15784530]

If the GO term “non-apoptotic programmed cell death” is merged with its parent, “programmed cell death” (PCD) (see below), then this current GO term would be made a child of PCD and a sibling to GO term “apoptosis”

7) GO:0016244 – non-apoptotic programmed cell death Midori has suggested that this term is not ontologically desirable and should be obsoleted. I [Candace] have no problem with that, although the term is currently somewhat useful – as described in PMID:15784530, sometimes one can tell that a type of PCD is not apoptotic but not what specific alternative type it is; the authors expect more different types of PCD to be described eventually. That much information [i.e. programmed cell death, but not apoptotic] is actually useful. And, there are currently 24 annotations to it. Alex Diehl has suggested that this term be merged with its parent term (programmed cell death). Alex, “This eliminates the term but preserves the annotations in an ontologically correct manner. Interested parties may go back and re-annotate to one of the new terms if they choose.” [This seems like a good suggestion, and it seconds Midori’s suggestion.. If GO editors decide instead that the term should be kept, then at least Remove the synonym: “exact: type II programmed cell death” ]

8) GO:0012501 – programmed cell death Add the following “COMMENT: This GO term should be used to annotate genes in the organism undergoing the PCD. For annotating genes in another organism whose products modulate PCD in a host organism, see “GO: 0052040 - modulation by symbiont of host PCD.”

Original comment by: ccollmer

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Hi Candace,

thanks for all your work putting this together. The only small change I propose is for the definition of the new term 'oncosis'.Could we not use the word 'proinflammatory'? Using this for Dictyostelium, I'd feel more comfortable with what the authors in PMID used, 'prelethal'. Also, I'd include the energy depletion. Revised def:

1) New term – “Oncosis” Definition: “the prelethal pathway leading to cell death accompanied by cellular and organelle swelling, increased membrane permeability and depletion of cellular energy [source:GOC:cwc, PMID:15784530; PMID:1579367]”

Petra

Original comment by: pfey

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3 August 2007 Hi Petra,

Sorry not to have gotten back to you sooner, but I left for Italy for the XIII International Congress on Molecular Plant-Microbe Interactions the day you wrote.

I guess I'd like to hear what others think about the definition I sent in for "oncosis." It seems from the thorough Minireview by Fink and Cookson (PMID:15784530) that "proinflammatory " is an essential component of oncosis and how it differs from other forms of PCD. They stress "proinflammatory" in their definitions in Table 1, and also in the figure legend to Fig 2, which I thought was very helpful in understanding the different pathways to cell death. In that figure legend is a definition for oncosis that may be better than the one I sent originally, and it incorporates the "prelethal" that you'd like to see -- could we compromise and use that one (see below)?

"Oncosis: the prelethal pathway leading to cell death accompanied by cellular and organelle swelling and membrane breakdown, with the eventual release of inflammatory cellular contents."

What do you all think about that possibility?

Candace

Original comment by: ccollmer

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Hi Candace, Petra & Alex,

This may be only tangentially related, but there seems to be some expertise on cell death reflected in this thread, so ...

Could some of you also look at SF 1796128, which requests a term for cell death by mitotic catastrophe? Your insight would be much appreciated.

Thanks, midori

https://sourceforge.net/tracker/index.php?func=detail&aid=1796128&group\_id=36855&atid=440764

Original comment by: mah11

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Hi Candace and All,

I'm sorry it took so long to get back to this. In any case, I need a term and we need to come to conclusion on at least oncosis. However, since I need this term for Dicty and I have no idea what 'infalmmatory cellular content' really is. It's right, the review PMID 15784530 focuses a lot on inflammatory, but I'm not sure this is right, as Dicty seems to have this kind of cell death but inflammation in an amoeba? In any case, I wrote to the author of the dicty paper and an expert on cell death for advice. So please stay tuned!

Petra

Original comment by: pfey

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Hello,

I hear back from the expert and it doesn't make things simpler. It basically confirms Alex's and all our concerns that it's dangerous to decide on and define terms based on few papers. The expert basically says that this is a field with controversies, and that the basic current belief for mammalians is that there are three main cell death types, apoptosis, autophagic cell death and necrotic cell death. He also states that "All three types of cell death (at least apoptosis and necrosis, but this will probably be the case also for autophagic cell death) are programmed as to their course in the dying cell..", In terms of oncosis, he says "The term oncosis is less frequently used, I would tend to think that (unless there is in the future a demonstration of molecular differences) it is just necrosis, and the latter term should be used for the moment."

This gives me the impression that we should probably move very slowly on this (and we are already as even we couldn't agree..), and read more literature a maybe we have to wait as the experts still have different opinions.

I also got more references of recent papers to read, here they are:

Festjens N, Vanden Berghe T, Vandenabeele P. Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta. 2006 Sep-Oct;1757(9-10):1371-87. Epub 2006 Jul 8. Review. PMID: 16950166

Golstein P, Kroemer G. A multiplicity of cell death pathways. Symposium on apoptotic and non-apoptotic cell death pathways. EMBO Rep. 2007 Sep;8(9):829-33. Epub 2007 Jul 27. PMID: 17721445

Golstein P, Kroemer G. Cell death by necrosis: towards a molecular definition. Trends Biochem Sci. 2007 Jan;32(1):37-43. Epub 2006 Dec 1. Review. PMID: 17141506

Petra

Original comment by: pfey

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As I understand it, we left this because we were concerned about representing controversial opinions rather than consensus science.

A review has come out recently that is essentially exactly the community consensus we require: Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. It's PMID:18846107, with full text at http://www.nature.com/cdd/journal/v16/n1/full/cdd2008150a.html

The recommendations recognize four major types of cell death -- apoptosis, autophagic cell death, cornification, and necrosis -- and several tentatively-described "atypical cell death modalities". Oncosis is described as the cytoplasmic swelling characteristic of necrosis.

Based on this review, I think we can modify Candace's last proposal slightly. I can adjust definitions and synonyms to be consistent with the recommendations and descriptions in the review (including the biochemical features in Table 3), and use this structure:

cell death GO:0008219 [i]programmed cell death GO:0012501 [merge in GO:0016244 non-apoptotic pcd] --[i] apoptosis GO:0006915 --[i] autophagic cell death GO:0048102 --[i] cornification GO:new --[i] necrosis GO:new [synonyms: necrotic cell death (exact), oncosis (narrow) --[i] pyroptosis GO:new [i] mitotic catastrophe GO:new

Pyroptosis is given as one of the atypical death modes, with a description consistent with Candace's draft; I would leave out 'proinflammatory' and instead add a phrase such as 'may play a role in inflammatory reactions'. I also wouldn't add most of the other minor types.

Let me know what you think! In light of more recent SF requests (see below), it would be nice to get this done. If future developments in the field mean we have to revisit cell death in a year or two, so be it. I will implement the above if there are no comments by the time I can get back to it, which will probably be a couple weeks from now.

Most other aspects of Candace's proposal -- comments and terms dealing with hosts and symbionts -- have been implemented.

Note that this also addresses SFs 1796128 and 2492121.

https://sourceforge.net/tracker/index.php?func=detail&aid=1796128&group\_id=36855&atid=440764 https://sourceforge.net/tracker/index.php?func=detail&aid=2494121&group\_id=36855&atid=440764

cheers, m

Original comment by: mah11

[gocentral]

Hi Midori,

Thanks for getting back to this and it's good news. I will glance at the review (hopefully) soon, but I think this will be great, as so many people agreed and wrote this review together.

Petra

Original comment by: pfey

[gocentral]

Midori,

Thanks for spotting this new article. It sounds like a comprehensive review was done, so we ought to follow its recommendations. My only issue is concerning the word "necrosis," which has been widely applied in earlier literature to other types of cell death including apoptosis, as well as the death of whole tissues. I would prefer we make the term name "necrotic cell death" with "cellular necrosis" as an EXACT synonym. We should also include a comment such as "Note that the word necrosis has been widely used in earlier literature to describe forms of cell death which are now known by more precise terms, such as apoptosis." As an annotator I know that it is easy simply to match a term in a paper to a GO term without giving it much thought, and I really want people to think carefully about using this term when another term might be indicated by a careful reading of the paper.

Also should we make a specific term for "oncosis" under "necrosis"? It could be useful.

Thanks,

Alex

Original comment by: addiehl

[gocentral]

Alex - your suggestions sound fine; I'll see if I can find a definition to use for 'oncosis' as a separate term (part_of necrotic cell death, and is_a ...? should be able to figure out an is_a parent if I can define it).

m

Original comment by: mah11

[gocentral]

Possible definition for oncosis:

A cellular process that results in swelling of the cell body, and that is morphologically characteristic of necrotic cell death. [PMID: 18846107; PMID:17873035]

It would be part_of necrotic cell death and is_a cellular process.

Original comment by: mah11

[gocentral]

• milestone: --> TermGenie
• assigned_to: nobody --> gomidori

Original comment by: mah11

[gocentral]

Two points:

1) The new article, PMID:18846107, does suggest that some necrosis is a type of programmed cell death ("necroptosis", new reviews: PMID:19109884, PMID:18955972), but that other necrosis is accidental in nature. Whether accidental necrosis qualifies as a GO process at all is debatable, but presumably if an investigator can tie a gene product to a necrotic outcome, one could argue for the term. So should we move "necrotic cell death" up a level to be a sibling of "programmed cell death" and add "necroptosis" as a both a type of "necrotic cell death" and "programmed cell death"?

2) [pardon me for the repetitive nature of the following discussion] While "oncosis" is seemingly considered a morphological characteristic of necrotic cell death in the new article, other articles clearly identify it as a type of PCD. Perhaps oncosis should be a part_of to "necroptosis" (as indicated in PMID:18846107 and figure 1 of PMID:19109884, and an is_a to "positive regulation of cell size ; GO:0045793" since swelling is a change of cell size. Or perhaps "oncosis" should simply be a type of "necroptosis", or a synonym to "necrosoptosis"? PMID:18955972 does not identify cell swelling or oncosis as part of necroptosis, whereas PMID:18846107 and PMID:19109884 do. So it is either a part_of or a specialize type of "necroptosis", arguing for a separate term rather than a synonym.

On balance, I can accept it as a part_of to "necroptosis" rather than an is_a, but I would appreciate additional opinions.

Thanks,

Alex

Original comment by: addiehl

[gocentral]

1) It seems that accidental death is a bit outside the scope of GO, but I don't have strong feelings. We can use 'necroptosis' as the name for programmed/controlled necrotic cell death whether we include accidental necrotic death or not.

2) The review with nomenclature recommendations is more recent than most of the papers I've looked at that refer to oncosis as a type of cell death. It would be nice to know whether the authors took that usage into account, but it does seem clear that they regard oncosis as a feature of necrotic cell death. Neither of the more recent reviews says much about oncosis, as far as I can tell. Taking all this into consideration, I don't see a strong case for making oncosis a type of cell death; I like the 'positive regulation of cell size' suggestion.

Any other opinions?

Original comment by: mah11

[gocentral]

Hi Everyone,

Sorry I've been late in responding - I had some trouble reconnecting with Sourceforge. I have not had time to carefully read the new review, but it is definitely most welcome. I would support Alex's suggestion that there be a term named "necrotic cell death," and that it be a sibling of "PCD." There are definitely genes that are tied to a necrotic outcome, especially in plant pathology, and it is not always known whether that is an outcome that is part of a plant defense strategy or part of a pathogen virulence strategy -- but neither of these is "accidental." Moreover, I think it's true that not all of necrotic cell death is "programmed" in nature, as in PCD. I also think that Alex's suggestion of where to put the term "necroptosis - as a child to 2 terms -- is good.

In terms of the term "oncosis," I am definitely not an expert here, so will not comment on what to do about that term.

Candace

Original comment by: ccollmer

[gocentral]

Hello,

I second Candace's comments and I also just had time to quickly go over the review. But as far as I can tell, this very recent review seems to be the most up-to-date information, plust it seems the whole cell death community agreed to write this together, as they found a need to clean up. Regarding oncosis, as they write it, it could be part_of necrotic cell death, defined as the swelling of the cell. And if needed at one point, another child could be added, 'cell rapture during necrosis' or something like it.

Petra

Original comment by: pfey

[gocentral]

Would this be a religious term?

Candace

Original comment by: ccollmer

[gocentral]

Great - one of these classical mistakes - just had to look up what rapture means, so quite the opposite of rupture - very nice! petra

Original comment by: pfey

[gocentral]

Wonderful malapropism. May we all be so lucky!

-- Alex

Original comment by: addiehl

[gocentral]

added necrotic cell death GO:0070265 necroptosis GO:0070266 oncosis GO:0070267 cornification GO:0070268 pyroptosis GO:0070269 mitotic catastrophe GO:0070270

refined defs GO:0006915, GO:0048102 merged 'non-apoptotic' terms into 'programmed cell death' parents GO:0016244 into GO:0012501 GO:0043070 into GO:0043067 GO:0043071 into GO:0043068 GO:0043072 into GO:0043069

note that there are a few merges yet to do, e.g. GO:0012503 into GO:0012502, so I'm not closing this until they're done

Original comment by: mah11

[gocentral]

finished merging 'non-apoptotic' terms into 'programmed cell death' parents: GO:0012503 into GO:0012502 GO:0012504 into GO:0052400 GO:0052397 into GO:0052400 GO:0052459 into GO:0052248 GO:0052152 into GO:0052040 GO:0052518 into GO:0052330 GO:0052153 into GO:0052042

closing at last!

Original comment by: mah11

[gocentral]

• status: open --> closed-accepted

Original comment by: mah11