Journal
CELL METABOLISM
Volume 2, Issue 5, Pages 309-319Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2005.10.003
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Funding
- NHLBI NIH HHS [P01 HL76491, R01 HL67725, P01 HL29582] Funding Source: Medline
- NIDDK NIH HHS [R01 DK58086, K08 DK65670] Funding Source: Medline
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Ferroxiclases 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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