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Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development

Author

Listed:
  • Juliane Tschuck

    (Helmholtz Zentrum München)

  • Vidya Padmanabhan Nair

    (Helmholtz Zentrum München)

  • Ana Galhoz

    (Helmholtz Zentrum München
    Ludwig-Maximilians University Munich)

  • Carole Zaratiegui

    (Helmholtz Zentrum München)

  • Hin-Man Tai

    (Helmholtz Zentrum München)

  • Gabriele Ciceri

    (Memorial Sloan Kettering Cancer Center)

  • Ina Rothenaigner

    (Helmholtz Zentrum München)

  • Jason Tchieu

    (Memorial Sloan Kettering Cancer Center
    Cincinnati Children’s Hospital Medical)

  • Brent R. Stockwell

    (Columbia University)

  • Lorenz Studer

    (Memorial Sloan Kettering Cancer Center)

  • Daphne S. Cabianca

    (Helmholtz Zentrum München)

  • Michael P. Menden

    (Helmholtz Zentrum München
    University of Melbourne)

  • Michelle Vincendeau

    (Helmholtz Zentrum München
    School of Medicine)

  • Kamyar Hadian

    (Helmholtz Zentrum München)

Abstract

The development of functional neurons is a complex orchestration of multiple signaling pathways controlling cell proliferation and differentiation. Because the balance of antioxidants is important for neuronal survival and development, we hypothesized that ferroptosis must be suppressed to gain neurons. We find that removal of antioxidants diminishes neuronal development and laminar organization of cortical organoids, which is fully restored when ferroptosis is inhibited by ferrostatin-1 or when neuronal differentiation occurs in the presence of vitamin A. Furthermore, iron-overload-induced developmental growth defects in C. elegans are ameliorated by vitamin E and A. We determine that all-trans retinoic acid activates the Retinoic Acid Receptor, which orchestrates the expression of anti-ferroptotic genes. In contrast, retinal and retinol show radical-trapping antioxidant activity. Together, our study reveals an unexpected function of vitamin A in coordinating the expression of essential cellular gatekeepers of ferroptosis, and demonstrates that suppression of ferroptosis by radical-trapping antioxidants or by vitamin A is required to obtain mature neurons and proper laminar organization in cortical organoids.

Suggested Citation

  • Juliane Tschuck & Vidya Padmanabhan Nair & Ana Galhoz & Carole Zaratiegui & Hin-Man Tai & Gabriele Ciceri & Ina Rothenaigner & Jason Tchieu & Brent R. Stockwell & Lorenz Studer & Daphne S. Cabianca & , 2024. "Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51996-1
    DOI: 10.1038/s41467-024-51996-1
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    References listed on IDEAS

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