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Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain.

Authors
  • Mukherjee, Chaitali1
  • Kling, Tina2
  • Russo, Belisa3
  • Miebach, Kerstin4
  • Kess, Eva3
  • Schifferer, Martina5
  • Pedro, Liliana D1
  • Weikert, Ulrich2
  • Fard, Maryam K5
  • Kannaiyan, Nirmal6
  • Rossner, Moritz6
  • Aicher, Marie-Louise7
  • Goebbels, Sandra7
  • Nave, Klaus-Armin7
  • Krämer-Albers, Eva-Maria4
  • Schneider, Anja8
  • Simons, Mikael9
  • 1 Institute of Neuronal Cell Biology, Technical University Munich, 80802 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany. , (Germany)
  • 2 Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany. , (Germany)
  • 3 German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany. , (Germany)
  • 4 Institute of Developmental Biology and Neurobiology (IDN), University of Mainz, 55128 Mainz, Germany. , (Germany)
  • 5 German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany. , (Germany)
  • 6 Department of Psychiatry, Ludwig-Maximillian University, 80336 Munich, Germany. , (Germany)
  • 7 Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany. , (Germany)
  • 8 German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Bonn, 53127 Bonn, Germany. Electronic address: [email protected] , (Germany)
  • 9 Institute of Neuronal Cell Biology, Technical University Munich, 80802 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany. Electronic address: [email protected] , (Germany)
Type
Published Article
Journal
Cell metabolism
Publication Date
Aug 04, 2020
Volume
32
Issue
2
Identifiers
DOI: 10.1016/j.cmet.2020.05.019
PMID: 32531201
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2020 Elsevier Inc. All rights reserved.

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