ArticleFree radical biology & medicine2018
Brain mitochondrial iron accumulates in Huntington's disease, mediates mitochondrial dysfunction, and can be removed pharmacologically.
Article in Free radical biology & medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Review: Quantitative Susceptibility Mapping (QSM) of Brain Iron Profile in Neurodegenerative Diseases.Frontiers in neuroscience · 2021Pooled it
- Ferroptosis and aging: Inducing and catalyzing neurodegenerative diseases.Neural regeneration research · 2026Article
- Ferroptosis in neurological diseases: moving towards therapeutic intervention.Molecular psychiatry · 2026Review
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 2026Review
- Targeting non-apoptotic regulated cell death (RCD) to treat neurodegenerative diseases.Acta pharmaceutica Sinica. B · 2026Review
- In Vivo Mapping of Catecholaminergic Loss and Iron Deposition in Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Roflumilast Elicits Therapeutic and Neuroprotective Effects in 3-Nitropropionic Acid-Induced Huntington's Disease-Like Neurodegeneration in Rats by Mitigating NLRP3 Inflammasome-Mediated Pyroptosis, Ferroptosis, and Glial Activation.Neurochemical research · 2026Article
- Metal ion dyshomeostasis in neurological disorders: from pathological mechanisms to targeted neuroprotective and regenerative strategies.Frontiers in pharmacology · 2026Review
- Homeostatic conflict as a driver for brain aging.Frontiers in genetics · 2026Review
- Targeting Aging and Diseases Associated with Ferroptosis and Senescence Through Modulation of Iron, Oxidative Stress and Lipid Peroxidation.Antioxidants (Basel, Switzerland) · 2025Review
- Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.MedComm · 2025Review
- Data Mining and Biochemical Profiling Reveal Novel Biomarker Candidates in Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Ferroptosis and Metabolic Dysregulation: Emerging Chemical Targets in Cancer and Infection.Molecules (Basel, Switzerland) · 2025Review
- Ferroptosis in cancer: revealing the multifaceted functions of mitochondria.Cellular and molecular life sciences : CMLS · 2025Review
- Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications.Antioxidants (Basel, Switzerland) · 2025Review
- Deferiprone ameliorates cisplatin induced peripheral neurotoxicity via ferritinophagy adjustment.Scientific reports · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Targeting Ferroptosis in Rare Neurological Disorders Including Pediatric Conditions: Innovations and Therapeutic Challenges.Biomedicines · 2025Review
- Gallic acid alleviates exercise-induced muscle damage by inhibiting mitochondrial oxidative stress and ferroptosis.Journal of translational medicine · 2025Article
- In defence of ferroptosis.Signal transduction and targeted therapy · 2025Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
Abstract
Mitochondrial bioenergetic dysfunction is involved in neurodegeneration in Huntington's disease (HD). Iron is critical for normal mitochondrial bioenergetics but can also contribute to pathogenic oxidation. The accumulation of iron in the brain occurs in mouse models and in human HD. Yet the role of mitochondria-related iron dysregulation as a contributor to bioenergetic pathophysiology in HD is unclear. We demonstrate here that human HD and mouse model HD (12-week R6/2 and 12-month YAC128) brains accumulated mitochondrial iron and showed increased expression of iron uptake protein mitoferrin 2 and decreased iron-sulfur cluster synthesis protein frataxin. Mitochondria-enriched fractions from mouse HD brains had deficits in membrane potential and oxygen uptake and increased lipid peroxidation. In addition, the membrane-permeable iron-selective chelator deferiprone (1 μM) rescued these effects ex-vivo, whereas hydrophilic iron and copper chelators did not. A 10-day oral deferiprone treatment in 9-week R6/2 HD mice indicated that deferiprone removed mitochondrial iron, restored mitochondrial potentials, decreased lipid peroxidation, and improved motor endurance. Neonatal iron supplementation potentiates neurodegeneration in mouse models of HD by unknown mechanisms. We found that neonatal iron supplementation increased brain mitochondrial iron accumulation and potentiated markers of mitochondrial dysfunction in HD mice. Therefore, bi-directional manipulation of mitochondrial iron can potentiate and protect against markers of mouse HD. Our findings thus demonstrate the significance of iron as a mediator of mitochondrial dysfunction and injury in mouse models of human HD and suggest that targeting the iron-mitochondrial pathway may be protective.
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