Davidson, Andrew J. and Heron, Rosalind and Das, Jyotirekha and Overholtzer, Michael and Wood, Will (2024) Ferroptosis-like cell death promotes and prolongs inflammation in Drosophila. Nature Cell Biology, 26 (9). pp. 1535-1544. ISSN 1465-7392

Abstract

Ferroptosis is a distinct form of necrotic cell death caused by overwhelming lipid peroxidation, and emerging evidence indicates a major contribution to organ damage in multiple pathologies. However, ferroptosis has not yet been visualized in vivo due to a lack of specific probes, which has severely limited the study of how the immune system interacts with ferroptotic cells and how this process contributes to inflammation. Consequently, whether ferroptosis has a physiological role has remained a key outstanding question. Here we identify a distinct, ferroptotic-like, necrotic cell death occurring in vivo during wounding of the Drosophila embryo using live imaging. We further demonstrate that macrophages rapidly engage these necrotic cells within the embryo but struggle to engulf them, leading to prolonged, frustrated phagocytosis and frequent corpse disintegration. Conversely, suppression of the ferroptotic programme during wounding delays macrophage recruitment to the injury site, pointing to conflicting roles for ferroptosis during inflammation in vivo.

People
Davidson, Andrew J.
Author

Davidson, Andrew J. and Heron, Rosalind and Das, Jyotirekha and Overholtzer, Michael and Wood, Will (2024) Ferroptosis-like cell death promotes and prolongs inflammation in Drosophila. Nature Cell Biology, 26 (9). pp. 1535-1544. ISSN 1465-7392

Heron, Rosalind and Amato, Clelia and Wood, Will and Davidson, Andrew J. (2023) Understanding the diversity and dynamics of in vivo efferocytosis: insights from the fly embryo. Immunological Reviews, 319 (1). pp. 27-44. ISSN 0105-2896

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Heron, Rosalind
Author

Davidson, Andrew J. and Heron, Rosalind and Das, Jyotirekha and Overholtzer, Michael and Wood, Will (2024) Ferroptosis-like cell death promotes and prolongs inflammation in Drosophila. Nature Cell Biology, 26 (9). pp. 1535-1544. ISSN 1465-7392

Heron, Rosalind and Amato, Clelia and Wood, Will and Davidson, Andrew J. (2023) Understanding the diversity and dynamics of in vivo efferocytosis: insights from the fly embryo. Immunological Reviews, 319 (1). pp. 27-44. ISSN 0105-2896

See full publications list
Das, Jyotirekha
Author

Davidson, Andrew J. and Heron, Rosalind and Das, Jyotirekha and Overholtzer, Michael and Wood, Will (2024) Ferroptosis-like cell death promotes and prolongs inflammation in Drosophila. Nature Cell Biology, 26 (9). pp. 1535-1544. ISSN 1465-7392

See full publications list
Overholtzer, Michael
Author

Davidson, Andrew J. and Heron, Rosalind and Das, Jyotirekha and Overholtzer, Michael and Wood, Will (2024) Ferroptosis-like cell death promotes and prolongs inflammation in Drosophila. Nature Cell Biology, 26 (9). pp. 1535-1544. ISSN 1465-7392

See full publications list
Wood, Will
Author

Davidson, Andrew J. and Heron, Rosalind and Das, Jyotirekha and Overholtzer, Michael and Wood, Will (2024) Ferroptosis-like cell death promotes and prolongs inflammation in Drosophila. Nature Cell Biology, 26 (9). pp. 1535-1544. ISSN 1465-7392

Heron, Rosalind and Amato, Clelia and Wood, Will and Davidson, Andrew J. (2023) Understanding the diversity and dynamics of in vivo efferocytosis: insights from the fly embryo. Immunological Reviews, 319 (1). pp. 27-44. ISSN 0105-2896

See full publications list
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