An atlas of ferroptosis-induced secretomes
Cells undergoing regulated necrosis systemically communicate with the immune system via the release of protein and non-protein secretomes. Ferroptosis is a recently described iron-dependent type of regulated necrosis driven by massive lipid peroxidation. While membrane rupture occurs during ferroptosis, a comprehensive appraisal of ferroptotic secretomes and their potential biological activity has been lacking. Here, we apply a multi-omics approach to provide an atlas of ferroptosis-induced secretomes and reveal a novel function in macrophage priming. Proteins with assigned DAMP and innate immune system function, such as MIF, heat shock proteins (HSPs), and chaperones, were released from ferroptotic cells. Non-protein secretomes with assigned inflammatory function contained oxylipins as well as TCA- and methionine-cycle metabolites. Interestingly, incubation of bone marrow-derived macrophages (BMDMs) with ferroptotic supernatants induced transcriptional reprogramming consistent with priming. Indeed, exposure to ferroptotic supernatants enhanced LPS-induced cytokine production. These results define a catalog of ferroptosis-induced secretomes and identify a biological activity in macrophage priming with important implications for the fine-tuning of inflammatory processes.
Authors
- Adriano B. Chaves‐Filho (ORCID: https://orcid.org/0000-0002-2321-6504)
- Christian Frezza (ORCID: https://orcid.org/0000-0002-3293-7397)
- Eric Seidel (ORCID: https://orcid.org/0000-0003-3334-3950)
- Silvia von Karstedt (ORCID: https://orcid.org/0000-0002-7816-5919)
- Ariadne Androulidaki
- Ali T. Abdallah (ORCID: https://orcid.org/0000-0002-8768-3232)
- Peter Kreuzaler (ORCID: https://orcid.org/0000-0001-8684-9424)
- Alina Dahlhaus (ORCID: https://orcid.org/0000-0001-9055-0695)
- Jan‐Wilm Lackmann (ORCID: https://orcid.org/0000-0001-8182-8034)
- Christina M. Bebber (ORCID: https://orcid.org/0000-0002-7841-7493)
- Christina Schmidt (ORCID: https://orcid.org/0000-0002-3867-0881)
- Fatma Isil Yapici (ORCID: https://orcid.org/0009-0004-9298-8315)
- Josephine Weber
- Julia Beck (ORCID: https://orcid.org/0009-0001-3683-0431)
- Almut Schulze (ORCID: https://orcid.org/0000-0002-8199-6422)
- Emin Güngör (ORCID: https://orcid.org/0009-0008-7244-1469)
- Min Yang (ORCID: https://orcid.org/0000-0002-9034-3175)
- Jenny Stroh
- Ioanna Kotouza
- Maria Nenchova
Institutions
- German Cancer Research Center (DE)
- University of Cologne (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- DKFZ-ZMBH Alliance (DE)
- University Hospital Cologne (DE)
Publication Details
- Journal
- Cell Death and Differentiation
- Published
- 2025-04-25
- DOI
- https://doi.org/10.1038/s41418-025-01517-4
- Citations
- 13
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 19.74