DIETARY IRON INTAKE MODULATES THE ACTIVITY OF IRON REGULATORY PROTEINS AND THE ABUNDANCE OF FERRITIN AND MITOCHONDRIAL ACONITASE IN RAT-LIVER

Iron regulatory protein 1 (IRP1) and IRP2 are cytoplasmic RNA binding proteins that coordinate cellular iron homeostasis in mammals, We inve stigated the effect of dietary iron intake on rat liver IRP activity i n relation to the abundance of two targets of IRP action, ferritin and mitochondrial aconitase (m-aconitase), Rats were fed diets containing 2, 11, 20, 37 (control), 72 or 107 mg iron/kg diet for 3 wk, RNA bind ing activity of IRP1 and IRP2 was enhanced one- to twofold in rats fed 11 or 2 mg iron/kg diet compared with control rats, IRP RNA binding a ctivity was inversely correlated to blood hemoglobin levels (r = -0.78 7; P < 0.0001), Compared with control rats, liver ferritin levels were depressed in rats fed 20 mg iron/kg diet and were undetectable in rat s ingesting diets with II or 2 mg iron/kg diet, Ferritin concentration s were biphasically related to IRP RNA binding activity with the regul ation of IRP occurring before the onset of ferritin accumulation. Iron deficiency caused up to a 50% decline in m-aconitase abundance, IRP R NA binding activity and m-aconitase abundance were inversely correlate d (r = -0.751; P < 0.0001), Our results indicate that (1) liver IRP ac tivity is responsive to a range of dietary iron levels, (2)there appea rs to be a differential effect of IRPs on ferritin and m-aconitase abu ndance, and (3) activation of IRPs may contribute to the alterations i n energy metabolism in iron deficiency through an impairment of m-acon itase synthesis.