Ferroptosis-like cell death promotes and prolongs inflammation in Drosophila Journal Article
| Authors: | Davidson, A. J.; Heron, R.; Das, J.; Overholtzer, M.; Wood, W. |
| Article Title: | Ferroptosis-like cell death promotes and prolongs inflammation in Drosophila |
| 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. © The Author(s) 2024. |
| Keywords: | immunohistochemistry; adult; controlled study; genetics; nonhuman; animal; metabolism; animals; animal tissue; cell death; apoptosis; immune system; confocal microscopy; embryo; bleaching; animal experiment; inflammation; drosophila; pathology; necrosis; transgenic animal; embryo, nonmammalian; chemotaxis; reactive oxygen metabolite; drosophila melanogaster; macrophage; phagocytosis; macrophages; tissue injury; drosophila proteins; lipid peroxidation; immunocompetent cell; lipocortin 5; drosophila protein; ultraviolet irradiation; animals, genetically modified; ferroptosis; article; depolarization; caco-2 cell line; nonmammalian embryo |
| Journal Title: | Nature Cell Biology |
| Volume: | 26 |
| Issue: | 9 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-09-01 |
| Start Page: | 1535 |
| End Page: | 1544 |
| Language: | English |
| DOI: | 10.1038/s41556-024-01450-7 |
| PUBMED: | 38918597 |
| PROVIDER: | scopus |
| PMCID: | PMC11392819 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
