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  • Perspective
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The role of regulated necrosis in endocrine diseases

Nature Reviews Endocrinology volume 17, pages 497–510 (2021)Cite this article

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Abstract

The death of endocrine cells is involved in type 1 diabetes mellitus, autoimmunity, adrenopause and hypogonadotropism. Insights from research on basic cell death have revealed that most pathophysiologically important cell death is necrotic in nature, whereas regular metabolism is maintained by apoptosis programmes. Necrosis is defined as cell death by plasma membrane rupture, which allows the release of damage-associated molecular patterns that trigger an immune response referred to as necroinflammation. Regulated necrosis comes in different forms, such as necroptosis, pyroptosis and ferroptosis. In this Perspective, with a focus on the endocrine environment, we introduce these cell death pathways and discuss the specific consequences of regulated necrosis. Given that clinical trials of necrostatins for the treatment of autoimmune conditions have already been initiated, we highlight the therapeutic potential of such novel therapeutic approaches that, in our opinion, should be tested in endocrine disorders in the future.

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Fig. 1: Regulated cell death pathways at a glance.
Fig. 2: Synchronized regulated necrosis.
Fig. 3: DAMPs and DIRE and the consequences of cell death.

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Acknowledgements

A.L. is supported by a Heisenberg-Professorship granted by the German Research Foundation (DFG), project number 324141047. Work in the Linkermann Lab and the Bornstein Lab is funded by Medical Clinic 3, University Hospital Carl Gustav Carus Dresden, Germany, and supported by the SFB-TRR 205, SFB-TRR 127 and the international research training group (IRTG) 2251. This work was further supported by the transCampus to S.R.B. and A.L.. N.P.K. was supported by the DFG, project KR3363/3-1. F.B. is supported by the Hochschulmedizin Zürich through the Flagship project Immuno-TarGET. We would like to thank all members of the Linkermann Lab for the ongoing discussions. We cordially thank R. Drtina for her assistance with preparing the first draft of the manuscript.

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  1. These authors contributed equally: Wulf Tonnus, Alexia Belavgeni.

Authors and Affiliations

  1. Clinic of Internal Medicine III, Division of Nephrology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany

    Wulf Tonnus, Alexia Belavgeni & Andreas Linkermann

  2. Medizinische Klinik und Poliklinik IV, Hospital of the Ludwig-Maximilian-University Munich, Munich, Germany

    Felix Beuschlein & Martin Reincke

  3. Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland

    Felix Beuschlein & Stefan R. Bornstein

  4. Clinic of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany

    Graeme Eisenhofer, Nils P. Krone & Stefan R. Bornstein

  5. Clinic of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital, University of Würzburg, Würzburg, Germany

    Martin Fassnacht & Matthias Kroiss

  6. Academic Unit of Child Health, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

    Nils P. Krone

  7. Diabetes and Nutritional Sciences, King’s College London, London, UK

    Stefan R. Bornstein

  8. Biotechnology Center, Technische Universität Dresden, Dresden, Germany

    Andreas Linkermann

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Contributions

W.T., A.B. and A.L. researched data for the article, contributed to the discussion of the content, wrote the article, and reviewed and/or edited the article before submission. F.B., G.E., M.F., M.K., N.P.K., M.R. and S.R.B. researched data for the article, contributed to the discussion of the content, and reviewed and/or edited the article before submission.

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Tonnus, W., Belavgeni, A., Beuschlein, F. et al. The role of regulated necrosis in endocrine diseases. Nat Rev Endocrinol 17, 497–510 (2021). https://doi.org/10.1038/s41574-021-00499-w

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