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NRI AT 20: CELL DEATH

Gasdermins: making pores for pyroptosis

Nature Reviews Immunology volume 21, pages 620–621 (2021)Cite this article

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A new form of programmed cell death was first observed in the 1980s in bacteria toxin-stimulated and bacteria-infected macrophages. This form of cell death was found to require caspase 1, which, like other caspases, was thought to be a mediator of apoptosis. However, unlike apoptosis, caspase 1-mediated cell death triggered potent inflammatory responses and was associated with cell swelling, plasma membrane rupture and release of cytoplasmic contents. On the basis of these features, Brad Cookson and his co-workers termed this form of cell death pyroptosis (in Greek, pyro means fire and ptosis means falling) to highlight its pro-inflammatory nature (Cookson et al., 2001). Later, pyroptosis was also found to be induced by mouse caspase 11 and human caspases 4 or 5 following recognition of lipopolysaccharide in the cytosol.

The study of apoptosis had suggested that there is not a single caspase substrate that critically controls the process of cell death. Yet, two studies published in 2015 suggested otherwise for pyroptosis (Shi et al., 2015; Kayagaki et al., 2015); a single gene Gsdmd, identified independently from CRISPR–Cas9 screens in macrophages and an N-ethyl-N-nitrosourea mutagenesis screen in mice, was shown to be critically required for both caspase 1-induced and caspase 11- or caspase 4-induced pyroptosis.

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References

Original articles

  • Shi, J. et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526, 660–665 (2015)

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  • Kayagaki, N. et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526, 666–671 (2015)

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Related articles

  • Cookson, B. T. & Brennan, M. A. Pro-inflammatory programmed cell death. Trends Microbiol. 9, 113–114 (2001)

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  • Shi, J. et al. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem. Sci. 42, 245–254 (2017)

    Article  CAS  Google Scholar 

  • Zhou, Z. et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science 368, eaaz7548 (2020)

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Authors and Affiliations

  1. National Institute of Biological Sciences, Beijing, PR China

    Feng Shao

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  1. Feng Shao
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Correspondence to Feng Shao.

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Shao, F. Gasdermins: making pores for pyroptosis. Nat Rev Immunol 21, 620–621 (2021). https://doi.org/10.1038/s41577-021-00602-2

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