Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization

DOI Web Site 148 Citations
  • Elizabeta Nemeth
    Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • Marie S. Tuttle
    Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • Julie Powelson
    Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • Michael B. Vaughn
    Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • Adriana Donovan
    Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • Diane McVey Ward
    Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • Tomas Ganz
    Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • Jerry Kaplan
    Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Abstract

<jats:p>Hepcidin is a peptide hormone secreted by the liver in response to iron loading and inflammation. Decreased hepcidin leads to tissue iron overload, whereas hepcidin overproduction leads to hypoferremia and the anemia of inflammation. Ferroportin is an iron exporter present on the surface of absorptive enterocytes, macrophages, hepatocytes, and placental cells. Here we report that hepcidin bound to ferroportin in tissue culture cells. After binding, ferroportin was internalized and degraded, leading to decreased export of cellular iron. The posttranslational regulation of ferroportin by hepcidin may thus complete a homeostatic loop: Iron regulates the secretion of hepcidin, which in turn controls the concentration of ferroportin on the cell surface.</jats:p>

Journal

  • Science

    Science 306 (5704), 2090-2093, 2004-12-17

    American Association for the Advancement of Science (AAAS)

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