Sci. STKE, 21 December 2004
METABOLISM Fundamentals of Iron Metabolism
The regulation of iron metabolism is a key component in maintaining health (see the Perspective by Beutler). Nemeth et al. show that hepcidin, a peptide hormone produced by the liver in response to iron loading and inflammation, binds directly to the iron exporter ferroportin. Internalization of ferroportin leads to its degradation and prevents the export of iron from the cells. Iron-overload diseases can be caused by the absence of hepcidin, and anemias can arise from increased production of hepcidin. Cells tightly regulate their responses to iron levels by using two proteins--iron regulatory protein (IRP) 1 and 2. Mice lacking IRP2 are severely compromised, but mice lacking IRP 1 appear normal. Meyron-Holtz et al. find that at physiological O2 levels, cells lacking IRP2 misregulate iron metabolism, whereas in cells cultured in high levels of O2--as commonly used in tissue culture--IRP1 can substitute for IRP2.
E. Nemeth, M. S. Tuttle, J. Powelson, M. B. Vaughn, A. Donovan, D. M. Ward, T. Ganz, J. Kaplan, Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306, 2090-2093 (2004). [Abstract] [Full Text]
Citation: Fundamentals of Iron Metabolism. Sci. STKE 2004, tw459 (2004).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882