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Description:
Iron and heme synthesis are intimately connected with erythropoiesis. The small hepatic peptide hormone hepcidin maintains transferrin saturation at physiological levels assuring adequate iron supplies to all cell types. Hepcidin is regulated by iron concentrations in plasma and the liver, inflammation, erythropoietic demand for iron and hypoxia. Iron needs to be carefully distributed inside the cells to the nucleus, cytosol and mitochondria for a variety of important physiological functions. Heme synthesis is the biological process that consumes the highest amount of iron. During this session, presenters will discuss these important physiological processes in normal and pathological conditions.
Dr. Muckenthaler will describe mechanisms that control hepcidin and ferroportin expression. Hepcidin orchestrates systemic iron fluxes and controls plasma iron levels by binding to the iron exporter ferroportin on the surface of iron releasing cells, triggering its degradation and hence reducing iron transfer to transferrin. Dr. Muckenthaler will also discuss pathologies that arise when this key regulatory circuitry is disrupted, in conditions such as iron deficiency or iron overload.
Dr. Gassmann will review the effect of hypoxia on iron metabolism and erythropoiesis. Iron plays a central role in adjusting to high altitude and it is involved in oxygen sensing processes, oxygen-dependent gene expression and oxygen-carrier molecules. Furthermore, erythropoietin (Epo) controls hepcidin expression via the erythroid factor called erythroferron (ErFe). Interestingly, ErFe is also expressed in the muscle. Dr. Gassmann will then describe additional studies that address the relationship between high altitude, iron and pulmonary hypertension, and how exercising mountaineer’s muscle may interfere with regulation of iron homeostasis.
Dr. Philpott will discuss the cellular machinery that mediates the distribution of iron within the cell. Proteins called iron chaperones distribute iron to cytosolic and nuclear iron enzymes, to the cytosolic iron-sulfur cluster machinery, and to the mitochondria for incorporation into heme and iron-sulfur clusters. Dr. Philpott will discuss the roles of poly-C binding proteins 1 and 2 and the monothiol glutaredoxin Glrx3. She will describe the flux of iron through erythropoietic cells, focusing on the role of PCBPs and ferritin in the delivery of iron to mitochondria for heme synthesis.