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Overexpression of the hereditary hemochromatosis protein, HFE, in HeLa cells induces an iron‐deficient phenotype
Author(s) -
Corsi Barbara,
Levi Sonia,
Cozzi Anna,
Corti Angelo,
Altimare Domenico,
Albertini Alberto,
Arosio Paolo
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01330-7
Subject(s) - transferrin , transferrin receptor , hereditary hemochromatosis , hemochromatosis , chemistry , ferritin , hela , microbiology and biotechnology , receptor , ceruloplasmin , deferoxamine , cell culture , biochemistry , biology , in vitro , genetics
A transfectant HeLa cell clone expressing HFE under the control of a tetracycline‐repressible promoter was generated. HFE expression was fully repressed by the presence of doxycycline, while it was strongly induced by growth in the absence of doxycycline. HFE accumulation was accompanied by a large (∼10‐fold) decrease in H‐ and L‐ferritin levels, by a ∼3–4‐fold increase in transferrin receptor, and a ∼2‐fold increase in iron regulatory protein activity. These indices of cellular iron deficiency were reversed by iron supplementation complexes. The overexpressed HFE immunoprecipitated together with transferrin receptor, indicating a physical association which is the likely cause for the observed ∼30% decrease in 55 Fe‐transferrin incorporation after 18 h incubation. In the HFE‐expressing cells the reduction in transferrin‐mediated iron incorporation was partially compensated by a ∼30% increase in non‐transferrin iron incorporation from 55 Fe‐NTA, evident after prolonged, 18 h, incubations. The findings indicate that HFE binding to transferrin receptor reduces cellular iron availability and regulates the balance between transferrin‐mediated and non‐transferrin‐mediated cellular iron incorporation.