![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Department of Nutritional Sciences, University of Wisconsin, Madison, WI 53706
4 To whom correspondence should be addressed. E-mail: eisenste{at}nutrisci.wisc.edu.
Iron regulatory proteins (IRP) modulate the use of mRNA-encoding proteins that are involved in the transport, storage and use of iron. Several new potential mRNA targets for IRP were recently identified: divalent metal transporter-1 (DMT-1) and ferroportin, which are critical regulators of iron absorption in the gut and of iron cycling between various tissues of the body. Although this may extend the reach of IRP to other processes that are important for maintaining body iron homeostasis, the extent to which IRP modulate other physiological processes that are altered in response to changes in iron availability is not clear. However, in the past several years, targets for IRP and IRP-like proteins were identified in eukaryotes and prokaryotes in the tricarboxylic acid (TCA) cycle and electron-transport chain. In mammals, this includes the mRNA that encodes the TCA-cycle enzyme mitochondrial aconitase (m-acon). Recent work established that m-acon expression is translationally regulated by iron in a manner that is strongly correlated with IRP RNA-binding activity. Interestingly, these studies also demonstrate that IRP regulate their mRNA targets in a hierarchical manner. The changes in m-acon synthesis and abundance in liver during iron deficiency fail to affect TCA-cycle capacity but are associated with a significant upregulation of mitochondrial export of radiolabeled citrate. We conclude that IRP are required for the regulation of physiological pathways that include but are not limited to iron metabolism, and as such, IRP are critical factors in the adaptive response to iron deficiency.
KEY WORDS: • iron • iron regulatory protein • ferritin • transferrin receptor
This article has been cited by other articles:
|
|
 |
|
  B. C. Jones, J. L. Beard, J. N. Gibson, E. L. Unger, R. P. Allen, K. A. McCarthy, and C. J. Earley Systems genetic analysis of peripheral iron parameters in the mouse Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R116 - R124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sanchez, B. Galy, T. Dandekar, P. Bengert, Y. Vainshtein, J. Stolte, M. U. Muckenthaler, and M. W. Hentze Iron Regulation and the Cell Cycle: IDENTIFICATION OF AN IRON-RESPONSIVE ELEMENT IN THE 3'-UNTRANSLATED REGION OF HUMAN CELL DIVISION CYCLE 14A mRNA BY A REFINED MICROARRAY-BASED SCREENING STRATEGY J. Biol. Chem., August 11, 2006; 281(32): 22865 - 22874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Theurl, V. Mattle, M. Seifert, M. Mariani, C. Marth, and G. Weiss Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease Blood, May 15, 2006; 107(10): 4142 - 4148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Anderson, K. Kirby, A. J. Hilliker, and J. P. Phillips RNAi-mediated suppression of the mitochondrial iron chaperone, frataxin, in Drosophila Hum. Mol. Genet., November 15, 2005; 14(22): 3397 - 3405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hieronymus and P. A. Silver A systems view of mRNP biology Genes & Dev., December 1, 2004; 18(23): 2845 - 2860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Pitula, K. M. Deck, S. L. Clarke, S. A. Anderson, A. Vasanthakumar, and R. S. Eisenstein Selective inhibition of the citrate-to-isocitrate reaction of cytosolic aconitase by phosphomimetic mutation of serine-711 PNAS, July 27, 2004; 101(30): 10907 - 10912. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Mayo, P. Kohlhepp, D. Zhang, and J. J. Winzerling Effects of sham air and cigarette smoke on A549 lung cells: implications for iron-mediated oxidative damage Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L866 - L876. [Abstract] [Full Text] [PDF]
|
|
