DIETARY IRON INTAKE RAPIDLY INFLUENCES IRON REGULATORY PROTEINS, FERRITIN SUBUNITS AND MITOCHONDRIAL ACONITASE IN RAT-LIVER

Iron regulatory protein 1 (IRP1) and IRP2 are cytoplasmic RNA binding proteins that are central regulators of mammalian iron homeostasis. We investigated the time-dependent effect of dietary iron deficiency on liver IRP activity in relation to the abundance of ferritin and the ir on-sulfur protein mitochondrial aconitase (macon), which are targets o f IRP action. Rats were fed a diet containing 2 or 34 mg iron/kg diet for 1-28 d. Liver IRP activity increased rapidly in rats fed the iron- deficient diet with IRP1 stimulated by d 1 and IRP2 by d 2. The maxima l activation of IRP2 was five-fold (d 7) and three-fold (d 4) for IRP1 . By d 4, liver ferritin subunits were undetectable and m-acon abundan ce eventually fell by 50% (P < 0.05) in iron-deficient rats. m-Acon ab undance declined most rapidly from d 1 to 11 and in a manner that was suggestive of a cause and effect type of relationship between IRP acti vity and m-acon abundance. In liver, iron deficiency did not decrease the activity of cytosolic aconitase, catalase or complex I of the elec tron transport chain nor was there an effect on the maximal rate of mi tochondrial oxygen consumption with the use of malate and pyruvate as substrates. Thus, the decline in macon abundance in iron deficiency is not reflective of a global decrease in liver iron-sulfur proteins nor does it appear to limit ATP production, Our results suggest a novel r ole for m-acon in cellular iron metabolism. We conclude that, in liver , iron deficiency preferentially affects the activities of IRPs and th e targets of IRP action.