Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves
Open accessAbstract
Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell–mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury. We also present evidence that myelinophagy is defective in the injured central nervous system. These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease.
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After nerve injury, Schwann cells oversee the capture of myelin debris in autophagosomes in a process termed myelinophagy.
“After nerve injury, Schwann cells oversee the capture of myelin debris in autophagosomes in a process termed “myelinophagy” [459,462,463],”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [463]
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- Authors
- Gomez-Sanchez, J. A., Carty, L., Iruarrizaga-Lejarreta, M., Palomo-Irigoyen, M., Varela-Rey, M., Griffith, M., Hantke, J., Macias-Camara, N., Azkargorta, M., Aurrekoetxea, I., De Juan, V. G., Jefferies, H. B. J., Aspichueta, P., Elortza, F., Aransay, A. M., Martínez-Chantar, M. L., Baas, F., Mato, J. M., Mirsky, R., Woodhoo, A., & Jessen, K. R.
- Affiliations
- University College London (GB)
- CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain 2
- CIC bioGUNE (ES)
- Instituto de Salud Carlos III (ES)
- University of the Basque Country (ES)
- The Francis Crick Institute (GB)
- Amsterdam UMC Location University of Amsterdam (NL)
- Ikerbasque (ES)
- Corresponding author
- Woodhoo, Ashwin
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2015-07-06
- Volume
- 210
- Issue
- 1
- Pages
- 153-168
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC4494002
- OpenAlex
- W1655540037
- Cited by
- 453
- References
- 49
- Citations by year
- 2026: 33 · 2025: 47 · 2024: 40 · 2023: 45 · 2022: 52 · 2021: 55 · 2020: 43 · 2019: 38 · 2018: 36 · 2017: 32 · 2016: 22 · 2015: 8
- FWCI
- 25.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by-nc-sa)
- Funders
- Wellcome Trust (FP7/2007–2013)
- Francis Crick Institute (10187)
- Cancer Research UK (15153)
- Instituto de Salud Carlos III
- National Center for Complementary and Integrative Health (R01AT001576)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- Schwann cells, selective autophagy, myelin debris clearance, nerve injury, Wallerian degeneration, JNK/c-Jun signaling, demyelinating disease, autophagosomes, myelin debris, central nervous system
- MeSH terms
- Animals, Autophagy, Cells, Cultured, Mice, Transgenic, Myelin Sheath, Sciatic Nerve, Wallerian Degeneration, Proto-Oncogene Proteins c-jun, JNK Mitogen-Activated Protein Kinases, Lipid Metabolism, TOR Serine-Threonine Kinases, Peripheral Nerve Injuries
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