Huntingtin: an iron-regulated protein essential for normal nuclear and perinuclear organelles
Open accessAbstract
Huntington's disease (HD), with its selective neuronal cell loss, is caused by an elongated glutamine tract in the huntingtin protein. To discover the pathways that are candidates for the protein's normal and/or abnormal function, we surveyed 19 classes of organelle in Hdh(ex4/5)/Hdh(ex4/5) knock-out compared with wild-type embryonic stem cells to identify any that might be affected by huntingtin deficiency. Although the majority did not differ, dramatic changes in six classes revealed that huntingtin's function is essential for the normal nuclear (nucleoli, transcription factor-speckles) and perinuclear membrane (mitochondria, endoplasmic reticulum, Golgi and recycling endosomes) organelles and for proper regulation of the iron pathway. Moreover, upmodulation by deferoxamine mesylate implicates huntingtin as an iron-response protein. However, excess huntingtin produced abnormal organelles that resemble the deficiency phenotype, suggesting the importance of huntingtin level to the protein's normal pathway. Thus, organelles that require huntingtin to function suggest roles for the protein in RNA biogenesis, trafficking and iron homeostasis to be explored in HD pathogenesis.
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In embryonic stem cells, huntingtin is iron-regulated and also involved in iron homoeostasis regulation.
“In embryonic stem cells, huntingtin is iron-regulated and also involved in iron homoeostasis regulation.193”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [193]
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References 36 · Cited by 226
Research works printed but not linked: 1
- Gutekunst C.-A.,, Levey, A., Heilman, C., Waley, W., Yi, H., Nash, N., Rees, H., Madden, J. and Hersch, S. (1995) Localization of huntingtin in rat, monkey and human tissues with anti-fusion protein antibodies. Proc. Natl Acad. Sci. USA, 92, 8710-8714.
- Authors
- Hilditch-Maguire, P.
- Affiliations
- Massachusetts General Hospital (US)
- Corresponding author
- Hilditch-Maguire, P.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-11-01
- Volume
- 9
- Issue
- 19
- Pages
- 2789-2797
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2162339143
- Cited by
- 226
- References
- 36
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 3 · 2015: 14 · 2014: 15 · 2013: 14 · 2012: 10
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Hereditary Disease Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS 16367, NS32765, R01NS032765)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- huntingtin, Huntington's disease, iron homeostasis, deferoxamine, nucleolus, mitochondria, endoplasmic reticulum, Golgi apparatus, recycling endosomes, organelle biogenesis, RNA biogenesis, RNA transport
- MeSH terms
- Huntingtin Protein, Exportin 1 Protein, Animals, Carrier Proteins, Cell Nucleus, Endoplasmic Reticulum, Fatty Acids, Unsaturated, Golgi Apparatus, Humans, Huntington Disease, Intracellular Membranes, Iron, Mitochondria, Nerve Tissue Proteins, Nuclear Proteins, Phenotype, Receptors, Transferrin, Endosomes, RNA, Stem Cells, Organelles, Gene Expression, Gene Deletion, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Active Transport, Cell Nucleus, Karyopherins, Mice
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