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. |
---|---|
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.) |
References: | Cell. 2008 Jan 11;132(1):137-48. (PMID: 18191227) Development. 2016 Jun 1;143(11):1981-92. (PMID: 27122166) J Cell Biol. 1964 Nov;23:307-25. (PMID: 14222816) Cell. 2004 Apr 30;117(3):285-97. (PMID: 15109490) Cell Mol Neurobiol. 2018 Mar;38(2):487-496. (PMID: 28447247) Annu Rev Neurosci. 1989;12:127-56. (PMID: 2648946) J Biol Chem. 2000 Feb 11;275(6):4305-10. (PMID: 10660599) Brain Res. 2004 Nov 12;1026(2):235-43. (PMID: 15488485) J Neurocytol. 1993 Nov;22(11):925-40. (PMID: 7507975) J Neurosci. 2002 Aug 1;22(15):6578-86. (PMID: 12151537) J Biol Chem. 2003 Jul 18;278(29):27144-8. (PMID: 12743117) iScience. 2018 Jun 29;4:190-203. (PMID: 30240740) Blood. 2018 Jan 18;131(3):342-352. (PMID: 29074498) Cell Death Dis. 2018 Feb 28;9(3):330. (PMID: 29491355) Prog Neurobiol. 2011 Mar;93(3):313-40. (PMID: 21216273) Acta Medica (Hradec Kralove). 2003;46(4):163-70. (PMID: 14965167) J Neurosci. 2006 Sep 20;26(38):9810-9. (PMID: 16988052) Cytoskeleton (Hoboken). 2012 Jul;69(7):486-95. (PMID: 22328339) Cold Spring Harb Perspect Biol. 2013 Aug 01;5(8):a011312. (PMID: 23906713) Pediatr Res. 1998 Sep;44(3):271-6. (PMID: 9727700) J Biol Chem. 2016 Sep 30;291(40):20827-20837. (PMID: 27497435) Antioxid Redox Signal. 2014 Aug 1;21(4):634-48. (PMID: 24409826) Clin Chim Acta. 2021 Feb;513:6-12. (PMID: 33309797) Neuron. 2016 Dec 21;92(6):1308-1323. (PMID: 28009276) J Lab Clin Med. 1998 Apr;131(4):306-15. (PMID: 9579383) Hum Mol Genet. 2014 Mar 15;23(6):1413-24. (PMID: 24154542) Neuron. 2017 Nov 1;96(3):651-666. (PMID: 29096078) J Cell Biol. 2013 Jul 22;202(2):351-64. (PMID: 23857772) J Neurosci. 2010 Mar 24;30(12):4232-40. (PMID: 20335458) Mol Biol Cell. 2006 Apr;17(4):2057-68. (PMID: 16467387) J Neurosci. 2009 Jan 21;29(3):610-9. (PMID: 19158288) Nat Rev Mol Cell Biol. 2005 Apr;6(4):345-51. (PMID: 15803140) J Comp Neurol. 2009 Jun 20;514(6):641-57. (PMID: 19363811) J Cell Biol. 2016 Jul 4;214(1):103-19. (PMID: 27268498) Methods Mol Biol. 2018;1739:329-337. (PMID: 29546717) Exp Neurol. 1982 Sep;77(3):634-43. (PMID: 7117467) Neuron. 2006 Aug 17;51(4):431-40. (PMID: 16908409) Trends Cell Biol. 2017 Jun;27(6):403-416. (PMID: 28228333) Glia. 1996 Jun;17(2):83-93. (PMID: 8776576) J Neurosci Res. 1998 Oct 15;54(2):147-57. (PMID: 9788274) Biochim Biophys Acta. 2010 Aug;1800(8):783-92. (PMID: 20176086) Cell Rep. 2013 Dec 26;5(6):1564-75. (PMID: 24332852) Neurobiol Dis. 2015 Sep;81:93-107. (PMID: 25724358) Front Cell Neurosci. 2019 Aug 09;13:373. (PMID: 31447650) Elife. 2018 Jan 30;7:. (PMID: 29381137) Microsurgery. 1998;18(2):119-24. (PMID: 9674927) J Neurosci. 2019 Jan 30;39(5):802-813. (PMID: 30523068) J Anat. 1953 Oct;87(4):387-406. (PMID: 13117757) J Neurosci. 2008 Nov 26;28(48):12736-47. (PMID: 19036966) Neuron. 2016 Dec 21;92(6):1294-1307. (PMID: 28009275) J Cell Sci. 2005 Dec 1;118(Pt 23):5411-9. (PMID: 16306220) J Biol Chem. 1997 Aug 8;272(32):20185-90. (PMID: 9242695) |
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 |
كن أول من يترك تعليقا!