Cited by 38Iron Metabolism and DisordersNeurological diseases and metabolismParkinson's Disease Mechanisms and Treatments

Characterization of the l-ferritin variant 460InsA responsible of a hereditary ferritinopathy disorder

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Cozzi, Anna, Santambrogio, Paolo, Corsi, Barbara, Campanella, Alessandro, Arosio, Paolo, Levi, Sonia·2006·Neurobiology of Disease

Abstract

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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Crossref · 10.1016/j.nbd.2006.05.004

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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
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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