Universität zu Köln

Yapici, F. Isil ORCID: 0009-0004-9298-8315, Seidel, Eric ORCID: 0000-0003-3334-3950, Dahlhaus, Alina ORCID: 0000-0001-9055-0695, Weber, Josephine, Schmidt, Christina ORCID: 0000-0002-3867-0881, de Britto Chaves Filho, Adriano, Yang, Ming ORCID: 0000-0002-7735-7804, Nenchova, Maria ORCID: 0009-0008-2522-9641, Güngör, Emre ORCID: 0009-0008-7244-1469, Stroh, Jenny, Kotouza, Ioanna, Beck, Julia ORCID: 0009-0001-3683-0431, Abdallah, Ali T., Lackmann, Jan-Wilm ORCID: 0000-0001-8182-8034, Bebber, Christina M. ORCID: 0000-0002-7841-7493, Androulidaki, Ariadne, Kreuzaler, Peter ORCID: 0000-0001-8684-9424, Schulze, Almut ORCID: 0000-0002-8199-6422, Frezza, Christian ORCID: 0000-0002-3293-7397 and von Karstedt, Silvia ORCID: 0000-0002-7816-5919 (2025). An atlas of ferroptosis-induced secretomes. Cell Death & Differentiation, 32 (11). pp. 1986-2008. Springer Nature. ISSN 1350-9047

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Abstract

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.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Yapici, F. Isil UNSPECIFIED https://orcid.org/0009-0004-9298-8315 UNSPECIFIED Seidel, Eric UNSPECIFIED https://orcid.org/0000-0003-3334-3950 UNSPECIFIED Dahlhaus, Alina UNSPECIFIED https://orcid.org/0000-0001-9055-0695 UNSPECIFIED Weber, Josephine UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Christina UNSPECIFIED https://orcid.org/0000-0002-3867-0881 UNSPECIFIED de Britto Chaves Filho, Adriano UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Ming UNSPECIFIED https://orcid.org/0000-0002-7735-7804 UNSPECIFIED Nenchova, Maria UNSPECIFIED https://orcid.org/0009-0008-2522-9641 UNSPECIFIED Güngör, Emre UNSPECIFIED https://orcid.org/0009-0008-7244-1469 UNSPECIFIED Stroh, Jenny UNSPECIFIED UNSPECIFIED UNSPECIFIED Kotouza, Ioanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Beck, Julia UNSPECIFIED https://orcid.org/0009-0001-3683-0431 UNSPECIFIED Abdallah, Ali T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lackmann, Jan-Wilm UNSPECIFIED https://orcid.org/0000-0001-8182-8034 UNSPECIFIED Bebber, Christina M. UNSPECIFIED https://orcid.org/0000-0002-7841-7493 UNSPECIFIED Androulidaki, Ariadne UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreuzaler, Peter UNSPECIFIED https://orcid.org/0000-0001-8684-9424 UNSPECIFIED Schulze, Almut UNSPECIFIED https://orcid.org/0000-0002-8199-6422 UNSPECIFIED Frezza, Christian UNSPECIFIED https://orcid.org/0000-0002-3293-7397 UNSPECIFIED von Karstedt, Silvia UNSPECIFIED https://orcid.org/0000-0002-7816-5919 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-801510
Identification Number:	10.1038/s41418-025-01517-4
Journal or Publication Title:	Cell Death & Differentiation
Volume:	32
Number:	11
Page Range:	pp. 1986-2008
Number of Pages:	23
Date:	25 November 2025
Publisher:	Springer Nature
ISSN:	1350-9047
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics Faculty of Medicine > Medizinische Statistik und Bioinformatik > Institut für Medizinische Statistik und Bioinformatik � IMSB Faculty of Medicine > Weitere > Translationale Genomik Zentrum für Molekulare Medizin
Subjects:	Data processing Computer science General statistics Life sciences Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80151