Regulation of iron metabolism in eukaryotes.
Iron metabolism is regulated in cells to ensure that iron supplies are adequate and nontoxic. The expression of iron metabolism is regulated primarily by posttranscriptional mechanisms. Ferritin, eALAS, SDHb of Drosophila, and mammalian mitochondrial aconitase are translationally regulated. The TfR is regulated at the level of mRNA stability. Iron regulatory proteins are regulated either by assembly or by disassembly of an iron-sulfur cluster (IRP1) or by rapid degradation in the presence of iron (IRP2). The list of targets for IRP-mediated regulation is growing longer, and a range of possibilities for versatile regulation exists, as each IRP can bind to unique targets that differ from the consensus IRE. The reactivity of iron with oxygen and the creation of toxic by-products may be the evolutionary stimulus that produced this system of tight posttranscriptional gene regulation.
Rouault
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Cell Biology and Metabolism National Institutes of Child and Human Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
Klausner
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D000154:Aconitate Hydratase / Q000737:chemistry; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005057:Eukaryotic Cells / Q000378:metabolism*; D019143:Evolution, Molecular; D005293:Ferritins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism
D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron; D000154:Aconitate Hydratase; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2