Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain
| Autor: | Nirmal Kannaiyan, Ulrich Weikert, Kerstin Miebach, Mikael Simons, Maryam K. Fard, Marie-Louise Aicher, Belisa Russo, Chaitali Mukherjee, Klaus-Armin Nave, Eva-Maria Krämer-Albers, Anja Schneider, Martina Schifferer, Moritz J. Rossner, Tina Kling, Liliana D. Pedro, Sandra Goebbels, Eva Kess |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Physiology Antioxidants Article metabolism [Oligodendroglia] 03 medical and health sciences Myelin Mice 0302 clinical medicine ddc:570 medicine Animals Secretion Receptor Cytotoxicity Molecular Biology Secretory pathway Neurons biology Chemistry metabolism [Apoferritins] Cell Biology biology.organism_classification Cell biology Ferritin Mice Inbred C57BL Oligodendroglia 030104 developmental biology medicine.anatomical_structure nervous system metabolism [Neurons] Apoferritins biology.protein metabolism [Antioxidants] Drosophila melanogaster 030217 neurology & neurosurgery Function (biology) |
| Zdroj: | Cell Metab Cell Metabolism Cell metabolism 32(2), 259-272.e10 (2020). doi:10.1016/j.cmet.2020.05.019 |
| ISSN: | 1932-7420 |
| DOI: | 10.1016/j.cmet.2020.05.019 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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