Os. Chen et al., DIETARY IRON INTAKE RAPIDLY INFLUENCES IRON REGULATORY PROTEINS, FERRITIN SUBUNITS AND MITOCHONDRIAL ACONITASE IN RAT-LIVER, The Journal of nutrition, 128(3), 1998, pp. 525-535
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.