QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ross, K. L. Articles by Eisenstein, R. S. Search for Related Content PubMed PubMed Citation Articles by Ross, K. L. Articles by Eisenstein, R. S.

---

Biochemical and Molecular Action of Nutrients

Iron Deficiency Decreases Mitochondrial Aconitase Abundance and Citrate Concentration without Affecting Tricarboxylic Acid Cycle Capacity in Rat Liver^{1 ,2}

Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706

³To whom correspondence should be addressed. E-mail: eisenste{at}nutrisci.wisc.edu.

Mitochondrial aconitase (m-acon) is the tricarboxylic acid (TCA) cycle enzyme that converts citrate to isocitrate. m-Acon mRNA is a potential target for regulation by iron regulatory proteins (IRPs), suggesting a link between dietary iron intake, m-acon synthesis, and energy metabolism. Our previous studies indicate that m-acon is one of a limited number of proteins that is down-regulated in iron-deficient liver. Here we use isolated hepatocytes to study the relationships among decreased m-acon abundance, TCA cycle function and cellular citrate concentration in iron deficiency. Rats were fed an iron-deficient (ID) (2 mg Fe/kg diet) diet, or they were pair-fed (PF) or freely fed (C) a control diet (50 mg Fe/kg diet) for up to 21 d. Hepatocyte total IRP activity was greater by d 2 in the ID group than in the C and PF groups and by d 10, the difference was maximal. Liver IRP activity was inversely correlated with m-acon abundance (r = -0.93, P < 0.0001). However, the decrease in m-acon abundance did not affect the ability of hepatocytes to oxidize 2-[¹⁴C]pyruvate or 1-[¹⁴C]acetate, indicating that TCA cycle capacity was not affected. Interestingly, by d 21, total liver citrate concentration was 40% lower in ID than in PF rats, suggesting enhanced utilization of citrate. However, the decrease in citrate concentration was not reflected in a change in liver total lipid concentration. Taken together, our results indicate that the iron-dependent regulation of m-acon in liver does not alter TCA cycle capacity but suggest that IRP-mediated changes in m-acon expression may modulate citrate use in other aspects of intermediary or iron metabolism.

KEY WORDS: • iron • iron regulatory proteins • mitochondrial aconitase • citrate • tricarboxylic acid cycle • rats

This article has been cited by other articles:

				J. P. McClung, N. E. Andersen, T. N. Tarr, C. H. Stahl, and A. J. Young Physical Activity Prevents Augmented Body Fat Accretion in Moderately Iron-Deficient Rats J. Nutr., July 1, 2008; 138(7): 1293 - 1297. [Abstract] [Full Text] [PDF]

				R. S. Eisenstein and K. L. Ross Novel Roles for Iron Regulatory Proteins in the Adaptive Response to Iron Deficiency J. Nutr., May 1, 2003; 133(5): 1510S - 1516. [Abstract] [Full Text] [PDF]

				V. R. Young Trace Element Biology: The Knowledge Base and its Application for the Nutrition of Individuals and Populations J. Nutr., May 1, 2003; 133(5): 1581S - 1587. [Abstract] [Full Text] [PDF]