TY - JOUR AU - Yapici, F Isil AU - Seidel, Eric AU - Dahlhaus, Alina AU - Weber, Josephine AU - Schmidt, Christina AU - de Britto Chaves Filho, Adriano AU - Yang, Ming AU - Nenchova, Maria AU - Güngör, Emre AU - Stroh, Jenny AU - Kotouza, Ioanna AU - Beck, Julia AU - Abdallah, Ali T AU - Lackmann, Jan-Wilm AU - Bebber, Christina M AU - Androulidaki, Ariadne AU - Kreuzaler, Peter AU - Schulze, Almut AU - Frezza, Christian AU - von Karstedt, Silvia TI - An atlas of ferroptosis-induced secretomes. JO - Cell death and differentiation VL - nn SN - 1350-9047 CY - [London] PB - Springer Nature M1 - DKFZ-2025-00882 SP - nn PY - 2025 N1 - epub / DKFZ-ZMBH Alliance AB - 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. LB - PUB:(DE-HGF)16 C6 - pmid:40281125 DO - DOI:10.1038/s41418-025-01517-4 UR - https://inrepo02.dkfz.de/record/300702 ER -