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The chemical basis of ferroptosis

Nature Chemical Biology volume 15, pages 1137–1147 (2019)Cite this article

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A Publisher Correction to this article was published on 02 January 2020

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Abstract

Lipid peroxidation underlies the mechanism of oxidative cell death now known as ferroptosis. This modality, distinct from other forms of cell death, has been intensely researched in recent years owing to its relevance in both degenerative disease and cancer. The demonstration that it can be modulated by small molecules in multiple pathophysiological contexts offers exciting opportunities for novel pharmacological interventions. Herein, we introduce the salient features of lipid peroxidation, how it can be modulated by small molecules and what principal aspects require urgent investigation by researchers in the field. The central role of non-enzymatic reactions in the execution of ferroptosis will be emphasized, as these processes have hitherto not been generally considered ‘druggable’. Moreover, we provide a critical perspective on the biochemical mechanisms that contribute to cell vulnerability to ferroptosis and discuss how they can be exploited in the design of novel therapeutics.

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Fig. 1: Lipid peroxidation occurs by a free-radical chain reaction (autoxidation) or enzymatic oxygenation.
Fig. 2: Key contributors to ferroptotic cell death.
Fig. 3: Inhibition of ferroptosis by radical-trapping antioxidants.
Fig. 4: Off-target RTA activity of lipoxygenase inhibitors.
Fig. 5: Key considerations for ferroptosis inhibition by radical-trapping antioxidants.
Fig. 6: Illustration of human diseases in which ferroptosis inhibitors/activators could modulate disease progression.

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  • 02 January 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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  1. These authors contributed equally: Marcus Conrad, Derek A. Pratt.

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  1. Helmholtz Zentrum München, Institute of Developmental Genetics, Neuherberg, Germany

    Marcus Conrad

  2. Department of Chemistry and Biomolecular Science, University of Ottawa, Ottawa, Canada

    Derek A. Pratt

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Conrad, M., Pratt, D.A. The chemical basis of ferroptosis. Nat Chem Biol 15, 1137–1147 (2019). https://doi.org/10.1038/s41589-019-0408-1

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