Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain.
axon-glia
ferritin
glia
iron
myelin
oligodendrocytes
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
04 08 2020
04 08 2020
Historique:
received:
17
01
2020
revised:
25
03
2020
accepted:
26
05
2020
pubmed:
13
6
2020
medline:
10
11
2021
entrez:
13
6
2020
Statut:
ppublish
Résumé
An evolutionarily conserved function of glia is to provide metabolic and structural support for neurons. To identify molecules generated by glia and with vital functions for neurons, we used Drosophila melanogaster as a screening tool, and subsequently translated the findings to mice. We found that a cargo receptor operating in the secretory pathway of glia was essential to maintain axonal integrity by regulating iron buffering. Ferritin heavy chain was identified as the critical secretory cargo, required for the protection against iron-mediated ferroptotic axonal damage. In mice, ferritin heavy chain is highly expressed by oligodendrocytes and secreted by employing an unconventional secretion pathway involving extracellular vesicles. Disrupting the release of extracellular vesicles or the expression of ferritin heavy chain in oligodendrocytes causes neuronal loss and oxidative damage in mice. Our data point to a role of oligodendrocytes in providing an antioxidant defense system to support neurons against iron-mediated cytotoxicity.
Identifiants
pubmed: 32531201
pii: S1550-4131(20)30300-4
doi: 10.1016/j.cmet.2020.05.019
pmc: PMC7116799
mid: EMS116661
pii:
doi:
Substances chimiques
Antioxidants
0
Apoferritins
9013-31-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
259-272.e10Subventions
Organisme : European Research Council
ID : 647168
Pays : International
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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