Selenoprotein I deficiency disrupts iron homeostasis in brain
- 1Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA
- 2Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Honolulu, HI 96813, USA
- 3Pacific Biosciences Research Center, University of Hawaii, Honolulu, HI 96813, USA
Abstract
Selenoprotein I (SELENOI) is an essential enzyme for phospholipid synthesis that catalyzes the production of plasmenyl-phosphatidylethanolamine (plasmenyl-PE), a key component of myelin that protects and insulates axons. We recently generated a mouse model of central nervous system-restricted SELENOI deficiency that recapitulates features observed in humans with rare loss-of-function SELENOI gene mutations such as motor deficits, diminished plasmenyl-PE, and hypomyelination. Crucially, myelin-producing oligodendrocytes have the highest concentration of iron among cell types in brain. Iron is a vital metal cofactor due to its contribution to redox reactions, but this property also predisposes it to generating reactive oxygen species via Fenton reactions. Moreover, an excess of redox-active iron promotes lipid peroxidation and increases susceptibility to cell death via ferroptosis. In this report, we show that SELENOI deficiency in mouse brain leads to ferroptosis in white matter tracts and promotes iron accumulation. These alterations are accompanied by oligodendrocyte proliferation and elevated numbers of ferritin-positive microglia in affected regions. Overall, our findings detail an intermittent cycle of oligodendrocyte death and proliferation that occurs when SELENOI is absent from the brain, resulting in accelerated iron accrual.
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BibTeX
@article{wurlitzer2026selenoprotein,
title = {{Selenoprotein I deficiency disrupts iron homeostasis in brain}},
author = {Karlin Wurlitzer and Chi Ma and Lance G.A. Nunes and Marissa Watanabe and Cole Griffin and Vedbar S. Khadka and Antonio G. Soares and Fukun W. Hoffmann and Peter R. Hoffmann and Matthew W. Pitts},
journal = {Neurobiology of disease},
year = {2026},
month = aug,
doi = {10.1016/j.nbd.2026.107588},
url = {https://doi.org/10.1016/j.nbd.2026.107588},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Selenoprotein I deficiency disrupts iron homeostasis in brain
AU - Karlin Wurlitzer
AU - Chi Ma
AU - Lance G.A. Nunes
AU - Marissa Watanabe
AU - Cole Griffin
AU - Vedbar S. Khadka
AU - Antonio G. Soares
AU - Fukun W. Hoffmann
AU - Peter R. Hoffmann
AU - Matthew W. Pitts
PY - 2026
DA - 2026/08/28
JO - Neurobiology of disease
DO - 10.1016/j.nbd.2026.107588
UR - https://doi.org/10.1016/j.nbd.2026.107588
AB - Selenoprotein I (SELENOI) is an essential enzyme for phospholipid synthesis that catalyzes the production of plasmenyl-phosphatidylethanolamine (plasmenyl-PE), a key component of myelin that protects and insulates axons. We recently generated a mouse model of central nervous system-restricted SELENOI deficiency that recapitulates features observed in humans with rare loss-of-function SELENOI gene mutations such as motor deficits, diminished plasmenyl-PE, and hypomyelination. Crucially, myelin-producing oligodendrocytes have the highest concentration of iron among cell types in brain. Iron is a vital metal cofactor due to its contribution to redox reactions, but this property also predisposes it to generating reactive oxygen species via Fenton reactions. Moreover, an excess of redox-active iron promotes lipid peroxidation and increases susceptibility to cell death via ferroptosis. In this report, we show that SELENOI deficiency in mouse brain leads to ferroptosis in white matter tracts and promotes iron accumulation. These alterations are accompanied by oligodendrocyte proliferation and elevated numbers of ferritin-positive microglia in affected regions. Overall, our findings detail an intermittent cycle of oligodendrocyte death and proliferation that occurs when SELENOI is absent from the brain, resulting in accelerated iron accrual.
SN - 0969-9961
SN - 1095-953X
ER -