Dual Role of ROS as Signal and Stress Agents: Iron Tips the Balance in favor of Toxic Effects

Figure 2

Simplified model of IRP-dependent regulation of intracellular iron homeostasis. The IRE/IRP machinery posttranscriptionally controls the expression of the major proteins of intracellular iron import (transferrin receptor, TfR1), export (ferroportin, Fpn), and storage (ferritin, Ft). Under conditions of iron excess in the labile iron pool (LIP), IRPs lose their RNA-binding capacity, and hence TfR1 mRNA is degraded (small arrow) while Fpn and Ft mRNAs are actively translated (big arrow and circle, resp.). The opposite occurs under conditions of iron deficiency: IRP1 and IRP2 binding to iron responsive elements (IREs) stabilize TfR1 mRNA (big arrow) and prevent the translation of Fpn and Ft mRNAs (small arrow and circle, resp.); this response increases iron availability.