Editors' ChoiceIRON METABOLISM

Iron Sensor

Science Signaling  03 Nov 2009:
Vol. 2, Issue 95, pp. ec355
DOI: 10.1126/scisignal.295ec355

Intracellular iron is an essential cofactor for many proteins but can also damage macromolecules, so its levels are carefully controlled. Cellular iron homeostasis is mediated by iron regulatory proteins that regulate the expression of genes involved in iron uptake and storage. However, it is not clear how cells sense iron bioavailability (see the Perspective by Rouault). Using different approaches, Salahudeen et al. and Vashisht et al. have identified the F-box protein FBXL5 as a human iron sensor. FBXL5 is part of an E3 ubiquitin ligase complex that regulates the degradation of iron regulatory proteins and thereby cellular iron levels. It contains a hemerythrin domain that binds iron and acts as an iron-dependent regulatory switch, causing the degradation of FBXL5 under low iron conditions. This alternative pathway for the regulation of iron homeostasis has implications for both normal cellular physiology and disease.

A. A. Salahudeen, J. W. Thompson, J. C. Ruiz, H.-W. Ma, L. N. Kinch, Q. Li, N. V. Grishin, R. K. Bruick, An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science 326, 722–726 (2009). [Abstract] [Full Text]

A. A. Vashisht, K. B. Zumbrennen, X. Huang, D. N. Powers, A. Durazo, D. Sun, N. Bhaskaran, A. Persson, M. Uhlen, O. Sangfelt, C. Spruck, E. A. Leibold, J. A. Wohlschlegel, Control of iron homeostasis by an iron-regulated ubiquitin ligase. Science 326, 718–721 (2009). [Abstract] [Full Text]

T. A. Rouault, An ancient gauge for iron. Science 326, 676–677 (2009). [Summary] [Full Text]