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Unexpected role of ceruloplasmin in intestinal iron absorption.

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Affiliations

  • 1. Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
      Authors
    • Cherukuri S 1
    (1 author)

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Cell Metabolism, 01 Nov 2005, 2(5):309-319
https://doi.org/10.1016/j.cmet.2005.10.003 PMID: 16271531 

Abstract 

Ferroxidases are essential for normal iron homeostasis in most organisms. The paralogous vertebrate ferroxidases ceruloplasmin (Cp) and hephaestin (Heph) are considered to have nonidentical functions in iron transport: plasma Cp drives iron transport from tissue stores while intestinal Heph facilitates iron absorption from the intestinal lumen. To clarify the function of Cp, we acutely bled Cp-/- mice to stress iron homeostasis pathways. Red cell hemoglobin recovery was defective in stressed Cp-/- mice, consistent with low iron availability. Contrary to expectations, iron was freely released from spleen and liver stores in Cp-/- mice, but intestinal iron absorption was markedly impaired. Phlebotomy of wild-type mice caused a striking shift of Cp from the duodenal epithelium to the underlying lamina propria, suggesting a critical function of Cp in basolateral iron transport. Regulated relocalization of intestinal Cp may represent a fail-safe mechanism in which Cp shares with Heph responsibility for iron absorption under stress.

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