Characterization of the l-ferritin variant 460InsA responsible of a hereditary ferritinopathy disorder
Open accessAbstract
Hereditary ferritinopathies are dominant inherited movement disorders associated with extensive alterations of the l-ferritin C-terminus peptide caused by nucleotide insertions in l-ferritin gene (FTL). We describe the characterization of the most common variant, produced by the 460InsA mutations and here named Ln1. The recombinant Ln1 assembled into 24-mer ferritin shells with low efficiency, however, it was able to form heteropolymers that showed a reduced capacity to incorporate iron in vitro. The Ln1 expressed in HeLa cells formed hybrid ferritins, with the endogenous H and L chains, and caused an iron excess phenotype. Ferritin inactivation and faster degradation in Ln1 transfectants concurred in increasing iron availability, which was probably responsible for the higher sensitivity to H(2)O(2) toxicity and higher level of oxidized proteins. The findings suggest that the pathogenic effects of Ln1 expression are more likely due to deregulation of cellular iron homeostasis rather than to protein conformational problems.
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Two different mutations in the ferritin L gene are linked to neurodegenerative conditions.
“Two different mutations in the ferritin L gene have been linked to neurodegenerative conditions (50, 62).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [62]
Histochemical analysis revealed abnormal ferritin and iron aggregates in this condition.
“Histochemical analysis revealed abnormal ferritin and iron aggregates (62).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [62]
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Self-citation
- Authors
- Cozzi, A., Santambrogio, P., Corsi, B., Campanella, A., Arosio, P., & Levi, S.
- Affiliations
- University of Brescia (IT)
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Levi, Sonia
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 23
- Issue
- 3
- Pages
- 644-652
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W1970788371
- Cited by
- 38
- References
- 35
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 1 · 2015: 2 · 2014: 4 · 2013: 4 · 2012: 1
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- L-ferritin, heteropolymers, iron incorporation, iron homeostasis, oxidative stress, protein degradation
- MeSH terms
- Central Nervous System, Ferritins, HeLa Cells, Homeostasis, Humans, Hydrogen Peroxide, Iron, Mutation, Peptides, Polymers, Protein Conformation, Recombinant Fusion Proteins, Down-Regulation, Oxidative Stress, Iron Metabolism Disorders, Gene Silencing, RNA Interference
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