title: Special delivery: distributing iron in the cytosol of mammalian cells.
abstract: Eukaryotic cells contain hundreds of proteins that require iron cofactors for activity. These iron enzymes are located in essentially every subcellular compartment; thus, iron cofactors must travel to every compartment in the cell. Iron cofactors exist in three basic forms: Heme, iron-sulfur clusters, and simple iron ions (also called non-heme iron). Iron ions taken up by the cell initially enter a kinetically labile, exchangeable pool that is referred to as the labile iron pool. The majority of the iron in this pool is delivered to mitochondria, where it is incorporated into heme and iron-sulfur clusters, as well as non-heme iron enzymes. These cofactors must then be distributed to nascent proteins in the mitochondria, cytosol, and membrane-bound organelles. Emerging evidence suggests that specific systems exist for the distribution of iron cofactors within the cell. These systems include membrane transporters, protein chaperones, specialized carriers, and small molecules. This review focuses on the distribution of iron ions in the cytosol and will highlight differences between the iron distribution systems of simple eukaryotes and mammalian cells.
authors.affiliation: Genetics and Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda, MD, USA.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Philpott
authors.affiliation: Genetics and Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda, MD, USA.
authors.forename: Moon-Suhn
authors.initials: MS
authors.lastname: Ryu
keywords: diiron; glutaredoxin; glutathione; iron chaperone; labile iron pool; metallochaperone; non-heme iron
references.citation: Anal Biochem. 2002 May 1;304(1):1-18
references.pmid: 11969183
references.citation: J Inherit Metab Dis. 2013 Jan;36(1):55-62
references.pmid: 22562699
references.citation: EMBO J. 2003 Aug 15;22(16):4082-90
references.pmid: 12912907
references.citation: Trends Biochem Sci. 2010 Jan;35(1):43-52
references.pmid: 19811920
references.citation: J Biol Chem. 2002 Jul 26;277(30):26944-9
references.pmid: 12011041
references.citation: Science. 2001 Jun 29;292(5526):2488-92
references.pmid: 11397910
references.citation: RNA. 2002 Mar;8(3):265-78
references.pmid: 12003487
references.citation: Science. 1999 Apr 30;284(5415):805-8
references.pmid: 10221913
references.citation: Nat Chem Biol. 2007 Mar;3(3):144-53
references.pmid: 17301803
references.citation: Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4043-8
references.pmid: 24591629
references.citation: Nature. 2005 Aug 18;436(7053):1035-39
references.pmid: 16110529
references.citation: Biol Chem. 2002 Mar-Apr;383(3-4):489-502
references.pmid: 12033438
references.citation: Cell Metab. 2010 Oct 6;12(4):373-385
references.pmid: 20889129
references.citation: Biochemistry. 2013 Nov 12;52(45):7926-42
references.pmid: 24180611
references.citation: J Clin Invest. 2010 May;120(5):1749-61
references.pmid: 20364084
references.citation: Brain. 2014 Feb;137(Pt 2):366-79
references.pmid: 24334290
references.citation: J Biol Chem. 1997 Sep 19;272(38):23469-72
references.pmid: 9295278
references.citation: J Biol Chem. 2008 Apr 18;283(16):10276-86
references.pmid: 18281282
references.citation: Biochemistry. 2009 Oct 13;48(40):9569-81
references.pmid: 19715344
references.citation: Dalton Trans. 2013 Mar 7;42(9):3220-9
references.pmid: 23232973
references.citation: Biochem J. 2014 Aug 15;462(1):25-37
references.pmid: 24854545
references.citation: Nature. 2000 Feb 17;403(6771):776-81
references.pmid: 10693807
references.citation: J Biol Inorg Chem. 2009 Jan;14(1):51-9
references.pmid: 18762996
references.citation: EMBO J. 2011 May 18;30(10):2044-56
references.pmid: 21478822
references.citation: J Biol Chem. 2013 Jun 14;288(24):17791-802
references.pmid: 23640898
references.citation: Protein Sci. 1993 Jun;2(6):1042-52
references.pmid: 8318889
references.citation: J Biol Chem. 2000 Jun 30;275(26):19906-12
references.pmid: 10747949
references.citation: J Biol Chem. 2006 Jun 30;281(26):17661-9
references.pmid: 16648636
references.citation: Mol Cell. 2008 May 23;30(4):393-402
references.pmid: 18498744
references.citation: Mol Biol Cell. 2002 Apr;13(4):1109-21
references.pmid: 11950925
references.citation: Biometals. 2011 Dec;24(6):1179-87
references.pmid: 21769609
references.citation: Cell Metab. 2011 Nov 2;14(5):647-57
references.pmid: 22055506
references.citation: Mol Cell. 2013 Jul 11;51(1):35-45
references.pmid: 23727016
references.citation: Sci STKE. 2007 Oct 09;2007(407):cm8
references.pmid: 17925579
references.citation: Am J Hum Genet. 2011 Oct 7;89(4):486-95
references.pmid: 21944046
references.citation: Nature. 2006 Mar 2;440(7080):96-100
references.pmid: 16511496
references.citation: Mol Biol Cell. 2013 Jun;24(12):1895-903
references.pmid: 23615448
references.citation: RNA. 2010 Aug;16(8):1449-62
references.pmid: 20584894
references.citation: Science. 2009 Oct 30;326(5953):722-6
references.pmid: 19762597
references.citation: Cell. 2010 Jun 11;141(6):1006-17
references.pmid: 20550936
references.citation: Biometals. 2012 Aug;25(4):711-23
references.pmid: 22350471
references.citation: Biochim Biophys Acta. 2012 Sep;1823(9):1468-83
references.pmid: 22610083
references.citation: Amino Acids. 2010 Feb;38(2):491-500
references.pmid: 19997760
references.citation: Curr Top Membr. 2012;70:169-214
references.pmid: 23177986
references.citation: Science. 2008 May 30;320(5880):1207-10
references.pmid: 18511687
references.citation: Cell Metab. 2009 Feb;9(2):152-64
references.pmid: 19147412
references.citation: J Biol Chem. 1995 Oct 13;270(41):24209-15
references.pmid: 7592626
references.citation: J Cell Sci. 2006 Nov 1;119(Pt 21):4554-64
references.pmid: 17074835
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13612-7
references.pmid: 16950869
references.citation: Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8031-6
references.pmid: 24843120
references.citation: J Biol Chem. 2010 Oct 15;285(42):32141-50
references.pmid: 20682781
references.citation: Science. 1997 Oct 31;278(5339):853-6
references.pmid: 9346482
references.citation: J Biol Chem. 2011 Jan 7;286(1):867-76
references.pmid: 20978135
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14814-9
references.pmid: 19706422
references.citation: Biol Trace Elem Res. 1984 Aug;6(4):357-64
references.pmid: 24264114
references.citation: Biochem Biophys Res Commun. 2010 Apr 2;394(2):372-6
references.pmid: 20226171
references.citation: Nat Chem Biol. 2008 Mar;4(3):152-6
references.pmid: 18277970
references.citation: Science. 2009 Oct 30;326(5953):718-21
references.pmid: 19762596
references.citation: Blood. 2007 Jul 1;110(1):125-32
references.pmid: 17376890
references.citation: Mol Cell. 2000 Feb;5(2):299-309
references.pmid: 10882071
references.citation: J Clin Invest. 2009 May;119(5):1159-66
references.pmid: 19352007
references.citation: Biochim Biophys Acta. 2010 Aug;1800(8):783-92
references.pmid: 20176086
references.citation: Biol Cell. 2004 Aug;96(6):407-11
references.pmid: 15384226
references.citation: J Biol Chem. 1995 Sep 15;270(37):21645-51
references.pmid: 7665579
references.citation: Proteins. 2007 Jul 1;68(1):123-30
references.pmid: 17393459
references.citation: Cell Metab. 2010 Sep 8;12(3):273-82
references.pmid: 20816093
references.citation: Curr Opin Chem Biol. 2011 Apr;15(2):284-90
references.pmid: 21216656
references.citation: Nature. 2009 Aug 13;460(7257):823-30
references.pmid: 19675642