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Cell death

STACKing the odds for discoveries

Nature Chemical Biology volume 17, pages 627–628 (2021)Cite this article

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Characterization of cell death kinetics identifies new on- and off-target small-molecule modulators of ferroptosis and reveals a role of amino acid metabolism in regulating ferroptosis sensitivity.

Elimination of damaged cells is integral to the maintenance of organismal homeostasis. Indeed, dysregulation of cell death is implicated in the pathophysiology of diseases such as neurodegeneration, autoimmune diseases, and cancer. While apoptosis is known to play an important role in embryogenesis and tumor suppression, it has become increasingly evident that other forms of cell death including autophagy, pyroptosis, necroptosis, and ferroptosis are also involved in these processes1. Execution of these pathways is often influenced by cell of origin, cell state, and lethal stimulus. However, leveraging this cellular plasticity for therapeutic benefit requires both understanding of the basic mechanisms of cell death execution and small-molecule modulators. To overcome this challenge, Conlon et al. used a high-throughput, time-lapse population cell death imaging assay to understand how cell death kinetics are affected by a library of small molecules2. This effort revealed new on- and off-target modulators of ferroptosis and identified drug repurposing candidates.

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Fig. 1: STACK reveals on- and off-target modulators of ferroptosis.

References

  1. Galluzzi, L. et al. Cell Death Differ. 25, 486–541 (2018).

    Article  Google Scholar 

  2. Conlon, M. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-021-00751-4 (2021).

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

    Article  CAS  Google Scholar 

  4. Soula, M. et al. Nat. Chem. Biol. 16, 1351–1360 (2020).

    Article  CAS  Google Scholar 

  5. Zhang, Y. et al. Cell Chem. Biol. 26, 623–633.e9 (2019).

    Article  CAS  Google Scholar 

  6. Ubellacker, J. M. et al. Nature 585, 113–118 (2020).

    Article  CAS  Google Scholar 

  7. Viswanathan, V. S. et al. Nature 547, 453–457 (2017).

    Article  CAS  Google Scholar 

  8. Fallahi-Sichani, M., Honarnejad, S., Heiser, L. M., Gray, J. W. & Sorger, P. K. Nat. Chem. Biol. 9, 708–714 (2013).

    Article  CAS  Google Scholar 

  9. Forcina, G. C., Conlon, M., Wells, A., Cao, J. Y. & Dixon, S. J. Cell Syst. 4, 600–610.e6 (2017).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA

    Mariluz Soula & Kıvanç Birsoy

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  1. Mariluz Soula
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  2. Kıvanç Birsoy
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Correspondence to Kıvanç Birsoy.

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The authors declare no competing interests.

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Soula, M., Birsoy, K. STACKing the odds for discoveries. Nat Chem Biol 17, 627–628 (2021). https://doi.org/10.1038/s41589-021-00743-4

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