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Regulation of cellular iron metabolism
review-article
24 February 2011
ferritin,
ferroportin,
iron-regulatory protein 1 (IRP1),
iron-regulatory protein 2 (IRP2),
iron–sulfur cluster (ISC),
transferrin receptor (TfR),
Abcb, ATP-binding cassette, subfamily B,
ALA, 5-aminolevulinic acid,
ALAS, ALA synthase,
β-APP, β-amyloid precursor protein,
BMP, bone morphogenetic protein,
c-aconitase, cytosolic aconitase,
C/EBPα, CCAAT/enhancer-binding protein α,
Cfd1, cytosolic Fe–S cluster-deficient protein 1,
Cul1, Cullin 1,
Dcytb, duodenal cytochrome b,
DHBA, dihydroxybenzoic acid,
DMT1, divalent metal transporter 1,
ER, endoplasmic reticulum,
FBXL5, F-box and leucine-rich repeat protein 5,
FLVCR, feline leukaemia virus, subgroup C, receptor,
Grx, glutaredoxin,
H, heavy,
HIF, hypoxia-inducible factor,
HO-1, haem oxygenase 1,
Hpx, haemopexin,
IOP1, iron-only hydrogenase-like protein 1,
IRE, iron-responsive element,
IRIDA, iron-refractory iron deficiency anaemia,
IRP, iron-regulatory protein,
ISC, iron–sulfur cluster,
CIA, cytosolic ISC assembly,
Isu, iron–sulfur cluster scaffold homologue,
L, light,
Lcn2, lipocalin 2,
LIP, labile iron pool,
m-aconitase, mitochondrial aconitase,
MRCKα, myotonic dystrophy kinase-related Cdc42 (cell division cycle 42)-binding kinase α ,
Nar1, nuclear architecture-related protein 1,
Nbp35, nucleotide-binding protein 35,
Nfs, nitrogen fixation homologue,
NTBI, non-transferrin-bound iron,
PCBP1, poly(rC)-binding protein 1,
Rbx1, Ring-box 1,
ROS, reactive oxygen species,
SDH, succinate dehydrogenase,
Skp1, S-phase kinase-associated protein 1,
SLC, solute carrier,
STAT3, signal transducer and activator of transcription 3,
Tf, transferrin,
TfR, Tf receptor,
UTR, untranslated region
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Abstract
Iron is an essential but potentially hazardous biometal. Mammalian cells require sufficient amounts of iron to satisfy metabolic needs or to accomplish specialized functions. Iron is delivered to tissues by circulating transferrin, a transporter that captures iron released into the plasma mainly from intestinal enterocytes or reticuloendothelial macrophages. The binding of iron-laden transferrin to the cell-surface transferrin receptor 1 results in endocytosis and uptake of the metal cargo. Internalized iron is transported to mitochondria for the synthesis of haem or iron–sulfur clusters, which are integral parts of several metalloproteins, and excess iron is stored and detoxified in cytosolic ferritin. Iron metabolism is controlled at different levels and by diverse mechanisms. The present review summarizes basic concepts of iron transport, use and storage and focuses on the IRE (iron-responsive element)/IRP (iron-regulatory protein) system, a well known post-transcriptional regulatory circuit that not only maintains iron homoeostasis in various cell types, but also contributes to systemic iron balance.
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Most cited references172
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Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.
Trude Flo, Kelly D. Smith, Shintaro Sato … (2004)
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The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition.
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A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.
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Author and article information
dhba, dihydroxybenzoic acid,iron-regulatory protein 2 (irp2),pcbp1, poly(rc)-binding protein 1,hpx, haemopexin,flvcr, feline leukaemia virus, subgroup c, receptor,stat3, signal transducer and activator of transcription 3,ala, 5-aminolevulinic acid,hif, hypoxia-inducible factor,slc, solute carrier,tfr, tf receptor,ntbi, non-transferrin-bound iron,isc, iron–sulfur cluster,sdh, succinate dehydrogenase,iron–sulfur cluster (isc),transferrin receptor (tfr),abcb, atp-binding cassette, subfamily b,nbp35, nucleotide-binding protein 35,cia, cytosolic isc assembly,cfd1, cytosolic fe–s cluster-deficient protein 1,er, endoplasmic reticulum,ferroportin,l, light,c/ebpα, ccaat/enhancer-binding protein α,fbxl5, f-box and leucine-rich repeat protein 5,iop1, iron-only hydrogenase-like protein 1,irp, iron-regulatory protein,lcn2, lipocalin 2,alas, ala synthase,tf, transferrin,dcytb, duodenal cytochrome b,β-app, β-amyloid precursor protein,isu, iron–sulfur cluster scaffold homologue,cul1, cullin 1,lip, labile iron pool,irida, iron-refractory iron deficiency anaemia,ferritin,nar1, nuclear architecture-related protein 1,ire, iron-responsive element,rbx1, ring-box 1,bmp, bone morphogenetic protein,dmt1, divalent metal transporter 1,m-aconitase, mitochondrial aconitase,iron-regulatory protein 1 (irp1),mrckα, myotonic dystrophy kinase-related cdc42 (cell division cycle 42)-binding kinase α,nfs, nitrogen fixation homologue,c-aconitase, cytosolic aconitase,ros, reactive oxygen species,h, heavy,utr, untranslated region,skp1, s-phase kinase-associated protein 1,ho-1, haem oxygenase 1,grx, glutaredoxin
dhba, dihydroxybenzoic acid, iron-regulatory protein 2 (irp2), pcbp1, poly(rc)-binding protein 1, hpx, haemopexin, flvcr, feline leukaemia virus, subgroup c, receptor, stat3, signal transducer and activator of transcription 3, ala, 5-aminolevulinic acid, hif, hypoxia-inducible factor, slc, solute carrier, tfr, tf receptor, ntbi, non-transferrin-bound iron, isc, iron–sulfur cluster, sdh, succinate dehydrogenase, iron–sulfur cluster (isc), transferrin receptor (tfr), abcb, atp-binding cassette, subfamily b, nbp35, nucleotide-binding protein 35, cia, cytosolic isc assembly, cfd1, cytosolic fe–s cluster-deficient protein 1, er, endoplasmic reticulum, ferroportin, l, light, c/ebpα, ccaat/enhancer-binding protein α, fbxl5, f-box and leucine-rich repeat protein 5, iop1, iron-only hydrogenase-like protein 1, irp, iron-regulatory protein, lcn2, lipocalin 2, alas, ala synthase, tf, transferrin, dcytb, duodenal cytochrome b, β-app, β-amyloid precursor protein, isu, iron–sulfur cluster scaffold homologue, cul1, cullin 1, lip, labile iron pool, irida, iron-refractory iron deficiency anaemia, ferritin, nar1, nuclear architecture-related protein 1, ire, iron-responsive element, rbx1, ring-box 1, bmp, bone morphogenetic protein, dmt1, divalent metal transporter 1, m-aconitase, mitochondrial aconitase, iron-regulatory protein 1 (irp1), mrckα, myotonic dystrophy kinase-related cdc42 (cell division cycle 42)-binding kinase α, nfs, nitrogen fixation homologue, c-aconitase, cytosolic aconitase, ros, reactive oxygen species, h, heavy, utr, untranslated region, skp1, s-phase kinase-associated protein 1, ho-1, haem oxygenase 1, grx, glutaredoxin