Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron is essential to life but it is poorly soluble in biological fluids and toxic in excess. Organisms have developed multiple proteins to insure iron transport and storage, and some of these have only been discovered recently. Among them, members of the Nramp family are transmembrane proteins which transport several divalent cations, including Fe2+. These proteins participate in intestinal iron absorption, erythopoiesis and microbial defence. Frataxin, which is deficient in Friedreich's ataxia, regulates iron flux through mitochondria. The intracellular labile iron pool, an intermediate form of iron between different subcellular compartments, regulates ferritin synthesis and stability of mRNA coding for proteins of iron transport. Subunit composition of ferritin plays an important role in the control of the size of this labile iron pool.
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PMID:[Intracellular iron metabolism]. 1098 40

Solute carrier 11a1 (Slc11a1; formerly Nramp1; where Nramp stands for natural-resistance-associated macrophage protein) is a proton/bivalent cation antiporter that localizes to late endosomes/lysosomes and controls resistance to pathogens. In the present study the role of Slc11a1 in iron turnover is examined in macrophages transfected with Slc11a1(Gly169) (wild-type) or Slc11a1(Asp169) (mutant=functional null) alleles. Following direct acquisition of transferrin (Tf)-bound iron via the Tf receptor, iron uptake and release was equivalent in wild-type and mutant macrophages and was not influenced by interferon-gamma/lipopolysaccharide activation. Following phagocytosis of [(59)Fe]Tf-anti-Tf immune complexes, iron uptake was equivalent and up-regulated similarly with activation, but intracellular distribution was markedly different. In wild-type macrophages most iron was in the soluble (60%) rather than insoluble (12%) fraction, with 28% ferritin (Ft)-bound. With activation, the soluble component increased to 82% at the expense of Ft-bound iron (<5%). In mutant macrophages, 40-50% of iron was in insoluble form, 50-60% was soluble and <5% was Ft-bound. Western-blot analysis confirmed failure of mutant macrophages to degrade complexes 24 h after phagocytic uptake. Confocal microscopy showed that complexes were within lysosome-associated membrane protein 1-positive vesicles in wild-type and mutant macrophages at 30 min and 24 h, implying failure in the degradative process in mature phagosomes in mutant macrophages. NO-mediated iron release was 2.4-fold higher in activated wild-type macrophages compared with mutant macrophages. Overall, our data suggest that iron acquired by phagocytosis and degradation is retained within the phagosomal compartment in wild-type macrophages, and that NO triggers iron release by direct secretion of phagosomal contents rather than via the cytoplasm.
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PMID:Solute carrier 11a1 (Slc11a1; formerly Nramp1) regulates metabolism and release of iron acquired by phagocytic, but not transferrin-receptor-mediated, iron uptake. 1190 51