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 iron-sulfur protein mitochondrial aconitase (m-acon), which are targets of 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 maximal 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 abundance eventually fell by 50% (P < 0.05) in iron-deficient rats. m-Acon abundance 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 activity and m-acon abundance. In liver, iron deficiency did not decrease the activity of cytosolic aconitase, catalase or complex I of the electron transport chain nor was there an effect on the maximal rate of mitochondrial oxygen consumption with the use of malate and pyruvate as substrates. Thus, the decline in m-acon 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 role for m-acon in cellular iron metabolism. We conclude that, in liver, iron deficiency preferentially affects the activities of IRPs and the targets of IRP action.
Chen
O S
OS
Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Blemings
K P
KP
Schalinske
K L
KL
Eisenstein
R S
RS
D000154:Aconitate Hydratase / Q000378:metabolism*; D000818:Animals; D004032:Diet; D005293:Ferritins / Q000378:metabolism*; D006454:Hemoglobins / Q000032:analysis; D007501:Iron / Q000008:administration & dosage* / Q000494:pharmacology; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats / Q000235:genetics; D017207:Rats, Sprague-Dawley; D051154:Wnt2 Protein
D006454:Hemoglobins; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D051154:Wnt2 Protein; D005293:Ferritins; D007501:Iron; D000154:Aconitate Hydratase; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2