دورية أكاديمية
Schwann Cells Provide Iron to Axonal Mitochondria and Its Role in Nerve Regeneration.
| العنوان: | Schwann Cells Provide Iron to Axonal Mitochondria and Its Role in Nerve Regeneration. |
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| المؤلفون: | Mietto BS; Centre for Research in Neuroscience, BRAiN program, Research Institute of the McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada.; Institute of Biological Sciences, Federal University of Juiz de Fora, Minas Gerais, Brazil., Jhelum P; Centre for Research in Neuroscience, BRAiN program, Research Institute of the McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada., Schulz K; Centre for Research in Neuroscience, BRAiN program, Research Institute of the McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada., David S; Centre for Research in Neuroscience, BRAiN program, Research Institute of the McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada sam.david@mcgill.ca. |
| المصدر: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2021 Aug 25; Vol. 41 (34), pp. 7300-7313. Date of Electronic Publication: 2021 Jul 16. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : Society for Neuroscience Original Publication: [Baltimore, Md.] : The Society, c1981- |
| مواضيع طبية MeSH: | Axons/*metabolism , Iron/*metabolism , Mitochondria/*metabolism , Nerve Regeneration/*physiology , Schwann Cells/*metabolism , Sciatic Neuropathy/*physiopathology, Animals ; Cation Transport Proteins/metabolism ; Cells, Cultured ; Ceruloplasmin/deficiency ; Ceruloplasmin/metabolism ; Female ; Ganglia, Spinal/cytology ; Iron Chelating Agents/pharmacology ; Mice ; Mice, Inbred C57BL ; Neuronal Outgrowth ; RNA/biosynthesis ; Ranvier's Nodes/metabolism ; Receptors, Transferrin/metabolism ; Sciatic Nerve/cytology ; Sciatic Nerve/physiology ; Sensory Receptor Cells/physiology ; Transcription, Genetic |
| مستخلص: | Iron is an essential cofactor for several metabolic processes, including the generation of ATP in mitochondria, which is required for axonal function and regeneration. However, it is not known how mitochondria in long axons, such as those in sciatic nerves, acquire iron in vivo Because of their close proximity to axons, Schwann cells are a likely source of iron for axonal mitochondria in the PNS. Here we demonstrate the critical role of iron in promoting neurite growth in vitro using iron chelation. We also show that Schwann cells express the molecular machinery to release iron, namely, the iron exporter, ferroportin (Fpn) and the ferroxidase ceruloplasmin (Cp). In Cp KO mice, Schwann cells accumulate iron because Fpn requires to partner with Cp to export iron. Axons and Schwann cells also express the iron importer transferrin receptor 1 (TfR1), indicating their ability for iron uptake. In teased nerve fibers, Fpn and TfR1 are predominantly localized at the nodes of Ranvier and Schmidt-Lanterman incisures, axonal sites that are in close contact with Schwann cell cytoplasm. We also show that lack of iron export from Schwann cells in Cp KO mice reduces mitochondrial iron in axons as detected by reduction in mitochondrial ferritin, affects localization of axonal mitochondria at the nodes of Ranvier and Schmidt-Lanterman incisures, and impairs axonal regeneration following sciatic nerve injury. These finding suggest that Schwann cells contribute to the delivery of iron to axonal mitochondria, required for proper nerve repair. SIGNIFICANCE STATEMENT This work addresses how and where mitochondria in long axons in peripheral nerves acquire iron. We show that Schwann cells are a likely source as they express the molecular machinery to import iron (transferrin receptor 1), and to export iron (ferroportin and ceruloplasmin [Cp]) to the axonal compartment at the nodes of Ranvier and Schmidt-Lanterman incisures. Cp KO mice, which cannot export iron from Schwann cells, show reduced iron content in axonal mitochondria, along with increased localization of axonal mitochondria at Schmidt-Lanterman incisures and nodes of Ranvier, and impaired sciatic nerve regeneration. Iron chelation in vitro also drastically reduces neurite growth. These data suggest that Schwann cells are likely to contribute iron to axonal mitochondria needed for axon growth and regeneration. (Copyright © 2021 the authors.) |
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| معلومات مُعتمدة: | Canada CIHR |
| فهرسة مساهمة: | Keywords: Schmidt-Lanterman incisures; Schwann cell; axon regeneration; iron; mitochondria; nodes of Ranvier |
| المشرفين على المادة: | 0 (Cation Transport Proteins) 0 (Iron Chelating Agents) 0 (Receptors, Transferrin) 0 (Tfrc protein, mouse) 0 (metal transporting protein 1) 63231-63-0 (RNA) E1UOL152H7 (Iron) EC 1.16.3.1 (Ceruloplasmin) |
| تواريخ الأحداث: | Date Created: 20210717 Date Completed: 20211203 Latest Revision: 20220226 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8387113 |
| DOI: | 10.1523/JNEUROSCI.0900-21.2021 |
| PMID: | 34272312 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1529-2401 |
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| DOI: | 10.1523/JNEUROSCI.0900-21.2021 |