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

Anna Cozzi, Paolo Santambrogio, Barbara Corsi, Alessandro Campanella, Paolo Arosio, Sonia Levi

Research output: Contribution to journalArticlepeer-review

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 H2O2 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.

Original languageEnglish
Pages (from-to)644-652
Number of pages9
JournalNeurobiology of Disease
Volume23
Issue number3
DOIs
Publication statusPublished - Sep 2006

Keywords

  • Ferritin
  • Hereditary ferritinopathy
  • Iron
  • Oxidative stress

ASJC Scopus subject areas

  • Neurology

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