Figure 8. Schematic overview of the mechanisms underlying the UPR-induced modulation of iron-related genes.

Activation of the PERK-dependent branch of the UPR modulates CHOP levels. This will in turn affect the C/EBPα protein pool and ultimately the stimulation of the hepcidin (HAMP) promoter. Regarding the other iron-genes, both ferritin H (FTH1) and ferroportin (FPN) display putative binding sites recognized by transcription factors (TFs) activated during the UPR. The presence of these regulatory elements may confer some UPR-responsiveness to ferritin H and ferroportin, increasing their expression in response to ER stress.