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Mukherjee, C., Kling, T., Russo, B., Miebach, K., Kess, E., Schifferer, M., Pedro, L.D., Weikert, U., Fard, M.K., Kannaiyan, N., Rossner, M., Aicher, M.L., Goebbels, S., Nave, K.A., Krämer-Albers, E.M., Schneider, A., Simons, M. (2020). Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain.  Cell Metab. 32(2): 259--272.e10.
FlyBase ID
FBrf0246370
Publication Type
Research paper
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.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Metab.
    Title
    Cell Metabolism
    Publication Year
    2005-
    ISBN/ISSN
    1550-4131
    Data From Reference