ArticleNeurobiology of disease2009
A novel transferrin/TfR2-mediated mitochondrial iron transport system is disrupted in Parkinson's disease.
Article in Neurobiology of disease, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.
- Efficacy of the iron-chelating agent, deferiprone, in patients with Parkinson's disease: A systematic review and meta-analysis.CNS neuroscience & therapeutics · 2024Pooled it
- Iron dyshomeostasis in neuropsychiatric disorders.Frontiers in psychiatry · 2026Review
- Ferroptosis in Parkinson's disease: a review of molecular mechanisms and emerging therapeutic strategies.Frontiers in neuroscience · 2026Review
- Environmental toxins in neurodegeneration - a narrative review.Neurological research and practice · 2025Review
- Multidimensional analysis of cerebral iron and vascular changes in chronic unilateral middle cerebral artery stenosis with quantitative susceptibility mapping, arterial spin labeling and high-resolution vessel wall imaging-a pilot study.Quantitative imaging in medicine and surgery · 2025Article
- Transferrin receptors.Experimental & molecular medicine · 2025Review
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Metabolic Parkinson's disease.Frontiers in aging neuroscience · 2025Review
- Article
- Uncovering Potential Biomarkers and Constructing a Prediction Model Associated with Iron Metabolism in Parkinson's Disease.Neuropsychiatric disease and treatment · 2025Article
- From pathogenesis to treatment: the emerging role of ferroptosis in Parkinson's disease.Frontiers in immunology · 2025Review
- Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects.Signal transduction and targeted therapy · 2024Review
- Ferroptosis-A Shared Mechanism for Parkinson's Disease and Type 2 Diabetes.International journal of molecular sciences · 2024Review
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.Neurotoxicology · 2024Review
- Quantitative susceptibility mapping of subcortical iron deposition in Parkinson disease and multiple system atrophy: clinical correlations and diagnostic implications.Quantitative imaging in medicine and surgery · 2024Article
- Brain Iron Dyshomeostasis and Ferroptosis in Alzheimer's Disease Pathophysiology: Two Faces of the Same Coin.Aging and disease · 2024Review
- Ultrastructural localization of Porphyromonas gingivalis gingipains in the substantia nigra of Parkinson's disease brains.NPJ Parkinson's disease · 2024Article
- Article
- Iron imbalance in neurodegeneration.Molecular psychiatry · 2024Review
- The Iron Metabolism with a Specific Focus on the Functioning of the Nervous System.Biomedicines · 2024Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
More than 80 years after iron accumulation was initially described in the substantia nigra (SN) of Parkinson's disease (PD) patients, the mechanisms responsible for this phenomenon are still unknown. Similarly, how iron is delivered to its major recipients in the cell - mitochondria and the respiratory complexes - has yet to be elucidated. Here, we report a novel transferrin/transferrin receptor 2 (Tf/TfR2)-mediated iron transport pathway in mitochondria of SN dopamine neurons. We found that TfR2 has a previously uncharacterized mitochondrial targeting sequence that is sufficient to import the protein into these organelles. Importantly, the Tf/TfR2 pathway can deliver Tf bound iron to mitochondria and to the respiratory complex I as well. The pathway is redox-sensitive and oxidation of Tf thiols to disulfides induces release from Tf of highly reactive ferrous iron, which contributes to free radical production. In the rotenone model of PD, Tf accumulates in dopamine neurons, with much of it accumulating in the mitochondria. This is associated with iron deposition in SN, similar to what occurs in PD. In the human SN, TfR2 is also found in mitochondria of dopamine neurons, and in PD there is a dramatic increase of oxidized Tf in SN. Thus, we have discovered a novel mitochondrial iron transport system that goes awry in PD, and which may provide a new target for therapeutic intervention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.