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Tschuck, J. ; Padmanabhan Nair, V. ; Galhoz, A. ; Zaratiegui, C. ; Tai, H.-M. ; Ciceri, G.* ; Rothenaigner, I. ; Tchieu, J.* ; Stockwell, B.R.* ; Studer, L.* ; Cabianca, D.S. ; Menden, M.P. ; Vincendeau, M. ; Hadian, K.

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

Nat. Commun. 15:7611 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Retinoic Acid; Dopamine Neurons; Derivation; Differentiation; Lineages; Platform
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 15, Heft: 1, Seiten: , Artikelnummer: 7611 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Signaling and Translation (SAT)
Institute of Virology (VIRO)
Institute of Computational Biology (ICB)
Institute of Functional Epigenetics (IFE)
Förderungen Deutsche Forschungsgemeinschaft
Deutsche Forschungsgemeinschaft (German Research Foundation)