What Does Iron Mean to an Oligodendrocyte?
Open accessAbstract
Iron is essential for life and plays a key role in multiple fundamental cellular functions. The brain has the highest rate of energy consumption, and within the brain, oligodendrocytes have the highest level of oxidative metabolism per volume. Oligodendrocytes also stain the strongest for iron. The high requirement for iron is related to an oligodendrocyte's primary function to produce the myelin sheath, which requires iron as a cofactor. In addition to the high‐energy demands that accompany the production of such dense and extensive membranous sheaths, iron is also required for lipid synthesis. Although the involvement of iron in oligodendrocyte functioning is clear, how iron is specifically acquired and utilized by oligodendrocytes is not completely understood. The purpose of this review is to provide a complete and thorough overview of the role of iron in oligodendrocytes. Here, we discuss in detail what is currently known about key iron transport proteins that participate in the balance of iron in oligodendrocytes. Understanding how oligodendrocytes utilize iron is beneficial in understanding dysmyelinating diseases, and the knowledge could be utilized to develop treatment options.
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Ferritin heavy chain-mediated iron delivery and storage are critical for oligodendrocyte iron metabolism and myelin lipid synthesis, helping to constrain iron-driven lipid peroxidation and ferroptotic death in white matter.
“ferritin heavy chain–mediated iron delivery and storage are critical for oligodendrocyte iron metabolism and myelin lipid synthesis, helping to constrain iron-driven lipid peroxidation and ferroptotic death in white matter [88, 89]”
From PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain (2026) · cites this paper as [89]
The H-Ferritin section describes FTH as an iron-delivery and storage protein for oligodendrocytes, explains that storage limits formation of harmful reactive oxygen species, and reports reduced myelin lipids when FTH levels are low. It does not establish the more specific claim that FTH constrains lipid peroxidation or ferroptotic death in white matter (searched: “lipid peroxidation” and “ferroptosis”). (LLM, conf=0.87)
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References 148 · Cited by 16
Research works printed but not linked: 2
- Escobar Cabrera, O. E., E. R. Bongarzone, E. F. Soto, and J. M. Pasquini. 1994. “ Single Intracerebral Injection of Apotransferrin in Young Rats Induces Increased Myelination.” Developmental Neuroscience 16, no. 5–6: 248– 254. 10.1159/000112116. 7768203 · DOI
- Li, Y., Q. Guan, Y. Chen, H. Han, W. Liu, and Z. Nie. 2013. “ Transferrin Receptor and Ferritin‐H Are Developmentally Regulated in Oligodendrocyte Lineage Cells.” Neural Regeneration Research 8, no. 1: 6. 10.4103/1673-5374.126960. 25206366 PMC4107500 · DOI
- Authors
- Wade, Q. W., & Connor, J. R.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Connor, James R.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2025-05-22
- Volume
- 73
- Issue
- 9
- Pages
- 1784-1804
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- PMC
- PMC12313010
- OpenAlex
- W4410600460
- Cited by
- 16
- References
- 148
- Citations by year
- 2026: 12 · 2025: 4
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Glia (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Pennsylvania State University
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- iron, oligodendrocytes, myelination, iron transport proteins, lipogenesis, oxidative metabolism, iron acquisition, brain iron metabolism
- MeSH terms
- Animals, Brain, Humans, Iron, Myelin Sheath, Oligodendroglia
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