Regulatory mechanisms of intestinal iron absorption-Uncovering of a fast-response mechanism based on DMT1 and ferroportin endocytosis

Knowledge on the intestinal iron transport process and the regulation of body iron stores has greatly increased during the last decade. The liver, through the sensing of circulating iron, is now recognized as the central organ in this regulation. High iron levels induce the synthesis of hepcidin, which in turn decreases circulating iron by inhibiting its recycling from macrophages and its absorption at the intestine. Another mechanism for the control of iron absorption by the enterocyte is an active Iron Responsive Element (IRE)/Iron Regulatory Protein (IRP) system. The IRE/IRP system regulates the expression of iron uptake and storage proteins thus regulating iron absorption. Similarly, increasing evidence points to the transcriptional regulation of both divalent metal transporter 1 (DMT1) and ferroportin expression. A new mechanism of regulation related to a phenomenon called the mucosa, block is starting to be unveiled. The mucosal block describes the ability of an initial dose of ingested iron to block absorption of a second dose given 2-4 h later. Here, we review the mechanisms involved in the expression of DMT1 and ferroportin, and present recent evidence on the molecular components and cellular processes involved in the mucosal block response. Our studies indicate that mucosal block is a fast-response endocytic mechanism destined to decrease intestinal iron absorption during a high ingest of iron.