Recommendations for robust and reproducible research on ferroptosis

Research output: Contribution to journalReview articleContributedpeer-review

Contributors

  • Eikan Mishima - , Tohoku University (Author)
  • Toshitaka Nakamura - , Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Sebastian Doll - , Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Bettina Proneth - , Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Maria Fedorova - , Center of Membrane Biochemistry and Lipid Research (Author)
  • Derek A Pratt - , University of Ottawa (Author)
  • José Pedro Friedmann Angeli - , University of Würzburg (Author)
  • Scott J Dixon - , Stanford University (Author)
  • Adam Wahida - , Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Marcus Conrad - , Technical University of Munich (Author)

Abstract

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.

Details

Original languageEnglish
Pages (from-to)615-630
Number of pages16
JournalNature Reviews Molecular Cell Biology
Volume26
Issue number8
Publication statusPublished - Aug 2025
Peer-reviewedYes

External IDs

Scopus 105002304261
ORCID /0000-0002-4692-3885/work/200630957

Keywords

Keywords

  • Ferroptosis/physiology, Humans, Animals, Iron/metabolism, Lipid Peroxidation, Reproducibility of Results