Overexpression of HFE in HepG2 cells reveals differences in intracellular distribution and co-localization of wt- and mutated forms Academic Article uri icon


MeSH Major

  • Amino Acid Substitution
  • Cytoplasm
  • Endosomes
  • Hemochromatosis
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Mutation, Missense


  • Liver is the primary target organ of Hereditary Hemochromatosis Type I, with the HFE mutations C282Y and H63D recognized as markers of this iron-overload disease. Hepatocytes are also the main site of synthesis of HFE. However, most early studies of overexpression of HFE were done in non-hepatic, non-HFE-expressing, cell lines. Here we report the setting up of a stable transfection model of wt- and mutant-HFE (H63D and C282Y) proteins in a hepatic cell line (HepG2), the analysis of its intracellular distribution and the effect of diferric transferrin on HFE localization. The C282Y mutant is retained in the ER, whereas HFE-wt and H63D co-localize with TfR1 exclusively in early recycling endosomes. Holotransferrin induces a re-localization of wt- and H63D-HFE, from early recycling endosomes to the cytoplasmic membrane. In conclusion our results establish the HepG2 cell line as a valuable model for the study of HFE.

publication date

  • July 2007



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.bcmd.2007.01.005

PubMed ID

  • 17428702

Additional Document Info

start page

  • 75

end page

  • 81


  • 39


  • 1