Disposal of iron by a mutant form of lipocalin 2

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 () and Andong Qiu ()
Additional contact information
Jonathan Barasch: Columbia University, Russ Berrie Medical Science Pavilion
Maria Hollmen: Columbia University, Russ Berrie Medical Science Pavilion
Rong Deng: Columbia University, Russ Berrie Medical Science Pavilion
Eldad A. Hod: Columbia University, Russ Berrie Medical Science Pavilion
Peter B. Rupert: Fred Hutchinson Cancer Research Center, University of Washington School of Medicine Biochemistry, Immunology
Rebecca J. Abergel: Lawrence Berkeley National Laboratory, BioActinide Chemistry Group
Benjamin E. Allred: Lawrence Berkeley National Laboratory, BioActinide Chemistry Group
Katherine Xu: Columbia University, Russ Berrie Medical Science Pavilion
Shaun F. Darrah: Columbia University, Russ Berrie Medical Science Pavilion
Yared Tekabe: Columbia University, Russ Berrie Medical Science Pavilion
Alan Perlstein: Columbia University, Russ Berrie Medical Science Pavilion
Rebecca Wax: Columbia University, Russ Berrie Medical Science Pavilion
Efrat Bruck: Columbia University, Russ Berrie Medical Science Pavilion
Jacob Stauber: Columbia University, Russ Berrie Medical Science Pavilion
Kaitlyn A. Corbin: Columbia University, Russ Berrie Medical Science Pavilion
Charles Buchen: Columbia University, Russ Berrie Medical Science Pavilion
Vesna Slavkovich: Columbia University, Russ Berrie Medical Science Pavilion
Joseph Graziano: Columbia University, Russ Berrie Medical Science Pavilion
Steven L. Spitalnik: Columbia University, Russ Berrie Medical Science Pavilion
Guanhu Bao: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Sciences, Anhui Agricultural University
Roland K. Strong: Fred Hutchinson Cancer Research Center, University of Washington School of Medicine Biochemistry, Immunology
Andong Qiu: Columbia University, Russ Berrie Medical Science Pavilion

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract Iron overload damages many organs. Unfortunately, therapeutic iron chelators also have undesired toxicity and may deliver iron to microbes. Here 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−/−) 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms12973 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12973

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms12973

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().