Home / FlashMed


Titolo Renal iron metabolism: transferrin iron delivery and the role of iron regulatory proteins
Autore D. Zhang, E. Meyron-Holtz, T.A. Rouault
Referenza J Am Soc Nephrol 2007; 18: 401-406
Contenuto In mammalian cells, iron is required for the function of many prosthetic groups, including heme and iron-sulfur clusters. Mammals absorb dietary iron and heme across the apical mucosa of duodenal epithelial cells using a Fe2_ transporter known as divalent metal transporter 1 (DMT-1; also known as solute carrier family 11 member 2, divalent cation transporter 1 (DCT1), and natural resistance associated macrophage protein 2) (1) or a specific heme transporter, heme carrier protein 1 (2). On the basolateral membrane, ferroportin (also known as mental transport protein 1 and iron regulated transporter 1) exports iron to the plasma (3), aided by hephaestin (4), which oxidizes ferrous (Fe2_) to ferric (Fe3_) iron. Serum transferrin (Tf), a 78-kD glycoprotein that is secreted mainly by the liver, binds one or two Fe3_ atoms. Each Fe3_ binds to four amino acid ligands from Tf and additionally binds a carbonate anion that stabilizes iron binding by providing two oxygen ligands. Carbonate binding completes occupancy of the six coordination positions of Fe3_ and thereby stabilizes binding of Fe3_ to Tf. Tf-bound iron circulates freely in the serum and extravascular spaces, and it serves as a source of iron for cells and tissues that are perfused by the systemic circulation, including liver, heart, muscle, kidney, and bone marrow (5). Excess intracellular iron is stored in ferritin, a heteropolymeric molecule that has a spherical shell structure and is composed of 24 H and L subunits, which can store up to 4500 iron atoms as a mineral core inside the shell (6). Iron can be released from ferritin when cells need more iron either when ferritin is degraded in the lysosome (7) or through a pore in the ferritin shell (8). Most cells modulate iron uptake by regulating the amount of Tf receptor 1 (TfR1) (9) that they express on the plasma membrane. The TfR functions as a dimer, and each 90-kD monomer has a single transmembrane-spanning domain. Upon binding iron-bearing Tf, the TfR-Tf complex is internalized into an early endosome, where acidification facilitates release of Fe3_ from Tf and a reductase reduces Fe3_ to Fe2_ (10), which then can be exported into cytosol by DMT-1 in the late endosomal/lysosomal compartment. A second TfR that is expressed mainly by hepatocytes, TfR2, is not regulated by intracellular iron levels and is unlikely to be important in renal iron metabolism (11).
Data 15.03.2007
Maggiori informazioni   
Lista completa