Accelerated Fe-S switch by a signaling pathway

By contrast to the delayed response pathways, IRPl induction by extracellular H2O2 via the fast response pathway may be caused by an accelerated turnover of the iron-sulfur cluster of IRPl. The experimental data discussed in Section 8.10 provide indirect evidence that extracellular H2O2 elicits a stress-response program, which results in IRPl induction by active removal of its cluster. In this context, it remains to be addressed whether the reported potential of IRPl (and IRP2) to become phosphorylated [156, 157] has functional significance. 

13 Physiological implications of IRPl regulation by oxidative stress 

The identification of H2O2 as a signaling molecule for IRPl establishes a direct regulatory link between iron metabolism and oxidative stress [140, 141]. The rapid and prolonged H202-mediated induction of IRPl to bind to IREs results in inhibition of ferritin mRNA translation and increased TfR mRNA levels [140]. These cellular responses are predicted to contribute to an increase in intracellular iron con- 

KP wishes to thank commanding oflScers of the Greek Army George Tzimanis and Vassilios Tsafarides for allowing time to develop this chapter while on military service. 

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