Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Ferroptosis

A radical way to avoid cell death

Nature Chemical Biology volume 19, pages 1–2 (2023)Cite this article

Subjects

Ferroptosis is a mechanism of cell death that has possible roles in numerous diseases. Two new studies have identified hydropersulfides as potent inhibitors of O2-dependent membrane damage and destruction, and as potential regulators of ferroptosis.

Unregulated cellular iron, unchecked lipid peroxidation and loss of membrane integrity can result in ferroptotic cell death, and this process can have possible pathological consequences (for example, neurodegeneration and cardiac disease). Although ferroptosis can have undesirable outcomes, this may not always be the case. Indeed, ferroptosis may actually have positive roles in, for example, tumor suppression and immune surveillance1. Thus, an understanding of the control and regulation of ferroptosis can be vital to a complete understanding of disease etiology whether ferroptosis is causative or protective. It is known that ferroptosis results from alterations in oxidation chemistry (that is, lipid peroxidation occurs via membrane oxidation) and therefore is a result of and represents a cellular oxidative stress. A cell that experiences oxidative stress may result in cellular components that undergo oxidative modification at thiols (RSH). As RSSH is oxidized with respect to RSH, its formation from RSH will also be more prevalent under cellular oxidative stress conditions. RSSH species, in particular, are potent one-electron reductants that are capable of quenching free radical chemistry that would otherwise be very destructive toward biological membranes. Sulfane sulfur species such as hydropersulfides and polysulfides are known to have antioxidative properties. Thus, it was proposed that RSSH levels may correlate with increased oxidative stress and ferroptosis.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: Mechanism of ferroptosis.

References

  1. Jiang, X., Stockwell, B. R. & Conrad, M. Nat. Rev. Mol. Cell Bio. 22, 266–282 (2021).

    Article  Google Scholar 

  2. Wu, Z., Khodade, V. S., Chauvin, J.-P. R., Rodriguez, D., Toscano, J. P. & Pratt, D. A. J. Am. Chem. Soc. 144, 15825–15837 (2022).

    Article  CAS  Google Scholar 

  3. Barayeu, U. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-022-01145-w (2022).

    Article  Google Scholar 

  4. Fukuto, J. M. & Hobbs, A. J. Nitric Oxide 107, 46–57 (2021).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Sonoma State University, Rohnert Park, CA, USA

    Jon M. Fukuto

  2. Department of Chemistry, Johns Hopkins University, Baltimore, MD, USA

    Jon M. Fukuto

Authors
  1. Jon M. Fukuto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jon M. Fukuto.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Fukuto, J.M. A radical way to avoid cell death. Nat Chem Biol 19, 1–2 (2023). https://doi.org/10.1038/s41589-022-01174-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41589-022-01174-5

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing