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A powerful cell-protection system prevents cell death by ferroptosis

The discovery of a mechanism that guards against a type of cell death called ferroptosis reveals a system that regenerates a ubiquitous protective component of biological membranes, and might offer a target for anticancer drugs.
  1. Brent R. Stockwell

    1. Brent R. Stockwell is in the Departments of Biological Sciences and of Chemistry, and at the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10027, USA.

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On 3 December 1956, the biochemist Frederick Crane detected, for the first time ever, a yellow substance purified from cow hearts, which had been obtained from the Oscar Mayer meat-processing factory in Madison, Wisconsin1. In the laboratory of David Green at the University of Wisconsin, Crane investigated the oily material he had discovered, and struck gold: he found a lipid molecule that has a crucial role in energy generation in cells. But there were hints that it might have another function. Now, writing in Nature, Doll et al.2 and Bersuker et al.3 report the discovery of this elusive role, finally revealing the missing part of the puzzle 63 years after Crane’s discovery.

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Nature 575, 597-598 (2019)

doi: https://doi.org/10.1038/d41586-019-03145-8

References

  1. Crane, F. L. Mitochondrion 7 (Suppl.), S2–S7 (2007).

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  2. Doll, S. et al. Nature 575, 693–698 (2019).

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  3. Bersuker, K. et al. Nature https://doi.org/10.1038/s41586-019-1705-2 (2019).

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  4. Dixon, S. J. et al. Cell 149, 1060–1072 (2012).

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  5. Stockwell, B. R. & Jiang, X. Cell Metab. 30, 14–15 (2019).

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  6. Hirschhorn, T. & Stockwell, B. R. Free Radic. Biol. Med. 133, 130–143 (2019).

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  7. Stockwell, B. R. et al. Cell 171, 273–285 (2017).

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  8. Yang, W. S. et al. Cell 156, 317–331 (2014).

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  9. Liu, H., Schreiber, S. L. & Stockwell, B. R. Biochemistry 57, 2059–2060 (2018).

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  10. Shimada, K. et al. Nature Chem. Biol. 12, 497–503 (2016).

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Competing Interests

B.R.S. holds equity in and serves as a consultant to Inzen Therapeutics, is an inventor on patents and patent applications related to ferroptosis, and has consulted with additional pharmaceutical and biotechnology companies in the past.

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