Disposal of iron by a mutant form of lipocalin 2 [electronic resource].
- Washington, D.C. : United States. Dept. of Energy. Office of Basic Energy Sciences, 2016. and Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy
- Physical Description:
- Article numbers 12,973 : digital, PDF file
- Additional Creators:
- Lawrence Berkeley National Laboratory, United States. Department of Energy. Office of Basic Energy Sciences, National Natural Science Foundation of China (NSFC), and United States. Department of Energy. Office of Scientific and Technical Information
- Iron overload damages many organs. Unfortunately, therapeutic iron chelators also have undesired toxicity and may deliver iron to microbes. In this work, we show that a mutant form (K3Cys) of endogenous lipocalin 2 (LCN2) is filtered by the kidney but can bypass sites of megalin-dependent recapture, resulting in urinary excretion. Because K3Cys maintains recognition of its cognate ligand, the iron siderophore enterochelin, this protein can capture and transport iron even in the acidic conditions of urine. Mutant LCN2 strips iron from transferrin and citrate, and delivers it into the urine. In addition, it removes iron from iron overloaded mice, including models of acquired (iron-dextran or stored red blood cells) and primary (Hfe<sup>-/-</sup>) iron overload. In each case, the mutants reduce redox activity typical of non-transferrin-bound iron. In summary, we present a non-toxic strategy for iron chelation and urinary elimination, based on manipulating an endogenous protein:siderophore:iron clearance pathway.
- Published through SciTech Connect., 10/31/2016., "ark:/13030/qt2m1415r6", Nature Communications 7 ISSN 2041-1723 AM, Jonathan Barasch; Maria Hollmen; Rong Deng; Eldad A. Hod; Peter B. Rupert; Rebecca J. Abergel; Benjamin E. Allred; Katherine Xu; Shaun F. Darrah; Yared Tekabe; Alan Perlstein; Rebecca Wax; Efrat Bruck; Jacob Stauber; Kaitlyn A. Corbin; Charles Buchen; Vesna Slavkovich; Joseph Graziano; Steven L. Spitalnik; Guanhu Bao; Roland K. Strong; Andong Qiu., March of Dimes, White Plains, NY (United States), and American Heart Association (AHA)
- Funding Information:
- AC02-05CH11231, R21 DK091729, R01DK073462, R01DK092684, 14GRNT18840098, and 81170654/H0507
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