TFR2, HFE, and HJV in the regulation of body iron homeostasis

Iron homeostasis is tightly regulated to balance essential physiological functions with the risk of iron toxicity. Hereditary hemochromatosis (HH) disrupts this balance, causing excessive dietary iron absorption and systemic iron overload. This thesis investigates the molecular mechanisms linking transferrin saturation sensing to BMP signaling in the liver, focusing on the roles of HFE, TFR2, and HJV. We demonstrate that these proteins form a complex required for BMP pathway activation and identify the cytoplasmic domain of TFR2 as critical for signaling. Additionally, we provide evidence for TFR2’s role in stress erythropoiesis, suggesting multifunctional roles in iron regulation and red blood cell production. These findings advance understanding of iron homeostasis and HH pathogenesis.