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Mishima, E. ; Nakamura, T. ; Doll, S. ; Proneth, B. ; Fedorova, M.* ; Pratt, D.A.* ; Friedmann Angeli, J.P.* ; Dixon, S.J.* ; Wahida, A. ; Conrad, M.

Recommendations for robust and reproducible research on ferroptosis.

Nat. Rev. Mol. Cell Biol., DOI: 10.1038/s41580-025-00843-2 (2025)
Postprint DOI PMC
Open Access Green
Ferroptosis is a necrotic, non-apoptotic cell death modality triggered by unrestrained iron-dependent lipid peroxidation. By unveiling the regulatory mechanisms of ferroptosis and its relevance to various diseases, research over the past decade has positioned ferroptosis as a promising therapeutic target. The rapid growth of this research field presents challenges, associated with potentially inadequate experimental approaches that may lead to misinterpretations in the assessment of ferroptosis. Typical examples include assessing whether an observed phenotype is indeed linked to ferroptosis, and selecting appropriate animal models and small-molecule modulators of ferroptotic cell death. This Expert Recommendation outlines state-of-the-art methods and tools to reliably study ferroptosis and increase the reproducibility and robustness of experimental results. We present highly validated compounds and animal models, and discuss their advantages and limitations. Furthermore, we provide an overview of the regulatory mechanisms and the best-studied players in ferroptosis regulation, such as GPX4, FSP1, SLC7A11 and ACSL4, discussing frequent pitfalls in experimental design and relevant guidance. These recommendations are intended for researchers at all levels, including those entering the expanding and exciting field of ferroptosis research.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Glutathione-peroxidase 4; Lipid-peroxidation; Nuclear Form; Cancer-cells; Expression; Gpx4; Transporter; Inhibition; Chain; Death
ISSN (print) / ISBN 1471-0072
e-ISSN 1471-0080
Journal Nature Reviews - Molecular Cell Biology
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Metabolism and Cell Death (MCD)
Grants
Food Science Institute Foundation (Ryoshoku Kenkyuukai)
Research Grant of Sapporo Bioscience Foundation
USA National Institutes of Health
Bundesministerium fur Bildung und Forschung
Saxon state parliament
SMWK
Natural Sciences and Engineering Research Council of Canada
European Research Council under the European Union
German Federal Ministry of Education and Research FERROPATH
Deutsche Forschungsgemeinschaft