Iron homeostasis translational

Iron homeostasis in mammalian cells is regulated by balancing iron uptake with intracellular storage and utilization. As we will see, this is largely achieved at the level of protein synthesis (translation of mRNA into protein) rather than at the level of transcription (mRNA synthesis), as was the case in microorganisms. This is certainly not unrelated to the fact that not only do microbial cells have a much shorter division time than mammalian cells, but that one consequence of this is that the half-life of microbial mRNAs is very much shorter (typically minutes rather than the hours or often days that we find with mammals). This makes it much easier to control levels of protein expression by changing the rate of specific mRNA synthesis by the use of inducers and repressors. So how do mammalian cells... 

The regulation of cellular iron homeostasis is to a large degree controlled at the level of the translation of the mRNAs of proteins involved in cellular iron metabolism (Rouault, 2006 Wallander et al., 2006). The key players in this post-transcriptional regulation are two iron regulatory proteins (IRPl and 1RP2), which function as... 

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.

In the next section we will outline briefly how IRPs control intracellular iron homeostasis by modulating ferritin mRNA translation and transferrin receptor mRNA stability [53,54]. 

Figure 1. Intracellular Iron Homeostasis. Iron transit across the cell surface membrane is mediated by (i) ferrotransferrin internalization by the transferrin receptor (TfR), (ii) DMT-1, (Hi) ferroportin mediated iron efflux from the duodenum into the blood. Ferritin mRNA translation is regulated by the modulated interaction between the IRPs and the IREs in the 5 UTR of ferritin mRNA. MAP kinase signaling events influence ferritin translation and transferrin receptor activity and expression.

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