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Redox homeostasis

A metabolic safety valve for reductive stress

Nature Metabolism (2026)Cite this article

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The glycerol-3-phosphate shuttle links redox balance to lipid synthesis, making the relief of reductive stress costly. Pan et al. rewire this circuit with a bifunctional enzyme that uncouples NAD⁺ regeneration from lipogenesis, restoring redox homeostasis under respiratory stress.

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Fig. 1: Engineering a metabolic safety valve to relieve reductive stress.

References

  1. Xie, N. et al. Sig. Transduct. Target. Ther. 5, 227 (2020).

    Article  CAS  Google Scholar 

  2. Yuan, X. et al. Commun. Biol. 3, 774 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. McReynolds, M. R., Chellappa, K. & Baur, J. A. Exp. Gerontol. 134, 110888 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yang, R., Guo, Z. & Li, B. Trends Cell Biol. https://doi.org/10.1016/j.tcb.2025.07.005 (2025).

    Article  PubMed  Google Scholar 

  5. Carballal, S. et al. J. Biol. Chem. 297, 100950 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pan, X. et al. Nat. Metab. https://doi.org/10.1038/s42255-025-01450-3 (2026).

    Article  Google Scholar 

  7. Erales, J. et al. Biochemistry 48, 6034–6040 (2009).

    Article  CAS  PubMed  Google Scholar 

  8. Driver, T. et al. Plant Physiol. 174, 2083–2097 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Russell, S., Wojtkowiak, J., Neilson, A. & Gillies, R. J. Sci. Rep. 7, 15285 (2017).

    Article  PubMed Central  Google Scholar 

  10. Inak, G. et al. Nat. Commun. 12, 1929 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mendelson, J. H. & Mello, N. K. Science 180, 1372–1374 (1973).

    Article  CAS  PubMed  Google Scholar 

  12. Li, B. et al. Sig. Transduct. Target. Ther. 10, 72 (2025).

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA

    Mahmoud S. Yahia & Melanie R. McReynolds

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  1. Mahmoud S. Yahia
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  2. Melanie R. McReynolds
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Correspondence to Melanie R. McReynolds.

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The authors declare no competing interests.

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Yahia, M.S., McReynolds, M.R. A metabolic safety valve for reductive stress. Nat Metab (2026). https://doi.org/10.1038/s42255-026-01463-6

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