Reduced iron export associated with hepcidin resistance can explain the iron overload spectrum in ferroportin disease.

ABSTRACT:

Background & aims

Ferroportin disease (FD) and hemochromatosis type 4 (HH4) are associated with variants in the ferroportin-encoding gene SLC40A1. Both phenotypes are characterized by iron overload despite being caused by distinct variants that either mediate reduced cellular iron export in FD or resistance against hepcidin-induced inactivation of ferroportin in HH4. The aim of this study was to assess if reduced iron export also confers hepcidin resistance and causes iron overload in FD associated with the R178Q variant.

Methods

The ferroportin disease variants R178Q andA77D and the HH4-variant C326Y were overexpressed in HEK-293T cells and subcellular localization was characterized by confocal microscopy and flow cytometry. Iron export and cytosolic ferritin were measured

SUBMITTER: Viveiros A 

PROVIDER: S-EPMC7496278 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature