Cytosolic iron regulatory protein

Iron regulatory proteins (IRPs) regulate the cellular iron level in mammalian cells. IRPs are known as cytosol mRNA binding proteins which control the stability or the translation rate of mRNAs of iron metabolism-related proteins such as TfR, ferritin, and 5-aminolevulinic acid synthetase in response to the availability of cellular iron [19-21] after uptake [5]. The regulatory mechanism involves the interaction between the iron-responsive element (IRE) in the 3 or 5 untranslated regions of the transcripts and cytosolic IRPs (IRP-1 and -2). IRP-1 is an iron-sulfur (Fe-S) protein with aconitase activity containing a cubane 4Fe-4S cluster. When Fe is replete, IRP-1 prevails in a 4Fe-4S form as a holo-form and is an active cytoplasmic aconitase. As shown in Fig. 3, when Fe is deplete, it readily loses one Fe from the fourth labile Fe in the Fe-S cluster to become a 3Fe-4S cluster and in this state has little enzymatic activity [22, 23]. 

Iron regulatory protein-1 (IRP-1) Iron sensor (cytosol aconitase)... 

Iron Regulatory Proteins 1 and 2 (IRPl and 2) are Important Cytosolic Iron Sensors that Regulate Expression of Ferritin, Transferrin Receptor and Other Iron Metabolism Proteins... 

Fig. (7). Hypothetical consequences of NO-mediated inhibition of plant cytosolic aconitase [208]. The interaction between NO and cytosolic aconitase triggers a cluster dissassembly and subsequently the inhibition of the catalytic activity of the enzyme. By analogy to mammalian studies, the resulting apoprotein may act as iron regulatory protein (1RP) and may modulate the translation of mRNA encoding proteins involved in the cellular iron homeostasis. The elevated free iron concentration promotes the Fenton reaction leading to hydroxyl radical (HO ) production. Both HO- and high concentrations of iron create a killing environment for host and pathogen.

Aconitase exists as both mitochondrial and cytosolic isoenzyme forms of similar structure. However, the cytosolic isoenzyme has a second function. In its apoenzyme form, which lacks the iron-sulfur cluster, it acts as the much-studied iron regulatory factor, or iron-responsive element binding protein (IRE-BP). This protein binds to a specific stem-loop structure in the messenger RNA for proteins involved in iron transport and storage (Chapter 28).86/9°... 

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