Pantopoulos, "Insights on regulation and function of the iron regulatory protein 1 (IRP1
)," Hemoglobin, vol.
In this study, M1 macrophages derived by recombinant IFN-[gamma] alone express high mRNA levels of hepcidin (Hamp2), FtH, and FtL and low levels of FPN, IRP1, and IRP2.
(a) Hamp2, (b) FPN, (c) FtH, (d) FtL, (e) IRP1, and (f) IRP2 mRNA levels in 24h cells after polarization.
The activity of IRP1 and IRP2 is dictated by the size of the cellular labile iron pool (LIP), a pool of iron in the low [micro]M range bound to low molecular weight compounds like citrate or glutathione , which is in continuous equilibrium with the sites of iron utilization or storage.
Both IRPs are homologous to the mitochondrial TCA cycle enzyme aconitase that converts citrate to isocitrate using an iron sulfur cluster (4Fe-4S) as a cofactor, but only IRP1 can assemble a cluster when sufficient iron is available, thus functioning as cytosolic aconitase, which is the prevailing form in most cells.
When there's less iron in the brain cell, IRP1
is more likely to hook up with the RNA, which prevents the production of APP.
During low-iron conditions, synthesis of both IRP1
and IRP2 increases.
Transgenic knockout mouse models of IRP1
, IRP2 indicate that the double knockout is embryonically lethal (52).
 demonstrated that upregulation of iron regulatory protein 1 (IRP1
) might be responsible for decreased expression of Fpn1 and increased cellular iron accumulation.