Deciphering the role of hepcidin in ferroptotic-mediated liver damage in hemochromatosis

Dr. Carolin Lohr,
Division for Gastroenterology, Hepatology and Infectiology, University Hospital Duesseldorf

Dr. Marlene leTertre,
Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg

Ferroptosis has recently been linked to the iron-mediated liver damage observed in hemochromatosis patients. This inherited iron overload disorder is due either to a defect in hepcidin expression (a small peptide that down-regulates the iron exporter ferroportin) or to a resistance of ferroportin to hepcidin. Interestingly, hemochromatosis patients with an hepcidin deficiency develop more severe liver damage. We suggest that the presence of hepcidin, acting beyond its iron-regulatory function, influences ferroptosis-mediated organ damage in haemochromatosis. To investigate this question, we will notably compare the effects of induced ferroptosis-mediated liver disease in two hemochromatosis mouse models that differ in hepcidin expression.