Iron species in iron homeostasis and toxicity.
Iron homeostasis in prokaryotic cells appears to be regulated essentially at the level of the genome by the Fur protein. When iron is in short supply the uptake and assimilation pathways are de-repressed and siderophores are synthesized together with the outer, inner (plasma) membrane, periplasmic and cytosolic components necessary for the uptake of ferri-siderophores. When iron is no longer limiting the Fe2+ the Fur complex acts as a transcriptional repressor, and shuts down the synthesis of all the components of iron assimilation. In euykarotic cells, iron homeostasis is dependent upon the iron regulatory factor (IRF), a cytoplasmic protein that can bind to specific stem loops, iron responsive elements (IREs) on the messenger ribonucleic acid molecules (mRNAs) of proteins involved in iron storage (ferritin), utilization (erythroid delta-aminolaevulinate synthase, AIS), and uptake (transferrin receptor). During ion depletion the IRE is in a high affinity form, which, by binding strongly to the corresponding mRNAs, down regulates iron storage and utilization, while up-regulating transferrin receptor expression. When the cells are iron replete, IRF binding to IREs is weak, allowing transferrin receptor mRNA to be degraded. In this paper it is shown that in physiological conditions of iron overload and depletion, IRF functions in vivo in the manner already described for in vitro models. The nature and the speciation of the various iron species within the low molecular weight pool of eukaryotic cells remains unclear.
Crichton
R R
RR
Unité de Biochimie, Catholique Université de Louvain-la-Neuve, Belgium.
Ward
R J
RJ
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D006706:Homeostasis; D007501:Iron / Q000378:metabolism* / Q000633:toxicity*; D035925:Iron-Regulatory Proteins; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism
D001426:Bacterial Proteins; D035925:Iron-Regulatory Proteins; D016601:RNA-Binding Proteins; D011990:Receptors, Transferrin; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D004247:DNA; D007501:Iron