Abstract
Cell death research was revitalized by the understanding that necrosis can occur in a highly regulated and genetically controlled manner. Although RIPK1 (receptor-interacting protein kinase 1)- and RIPK3–MLKL (mixed lineage kinase domain-like)-mediated necroptosis is the most understood form of regulated necrosis, other examples of this process are emerging, including cell death mechanisms known as parthanatos, oxytosis, ferroptosis, NETosis, pyronecrosis and pyroptosis. Elucidating how these pathways of regulated necrosis are interconnected at the molecular level should enable this process to be therapeutically targeted.
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Acknowledgements
The authors apologize to colleagues whose work was not discussed in this Opinion owing to space limitations. Research in the group of P.V. is supported by Belgian grants (Interuniversity Attraction Poles, IAP 7/32), Flemish grants (Research Foundation Flanders (FWO) G.0875.11, FWO G.0973.11, FWO G.0A45.12N, FWO G.0787.13N, Methusalem grant - BOF09/01M00709), Ghent University grants (MRP, GROUP-ID consortium, Belgium), a grant from the Foundation against Cancer, F94 and grants from the Flanders Institute for Biotechnology (VIB). H.W. is funded by a Cancer Research UK programme grant, an European Research Council (ERC) Advanced Grant and a Wellcome Trust Senior Investigator Award, UK. T.V.B. holds a postdoctoral fellowship from the FWO. A.L. is funded by the German Society for Nephrology, Novartis, Pfizer, Fresenius and the Hans-Werner Jackstädt Stiftung. S.J.L. is an omics@vib postdoctoral fellow at the VIB, co-funded by the Marie Curie COFUND initiative.
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H.W. is co-founder and shareholder of Apogenix GmbH (Heidelberg, Germany), a biotech company developing innovative drugs that target cell death and inflammatory pathways. T.V.B., A.L., S.J.L. and P.V. declare no competing interests.
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Berghe, T., Linkermann, A., Jouan-Lanhouet, S. et al. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol 15, 135–147 (2014). https://doi.org/10.1038/nrm3737
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DOI: https://doi.org/10.1038/nrm3737
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