Both laboratories contributed equally to this work.
Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE-expressing cells*
Article first published online: 14 DEC 2001
Copyright © 2002 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 190, Issue 2, pages 218–226, February 2002
How to Cite
Roy, C. N., Blemings, K. P., Deck, K. M., Davies, P. S., Anderson, E. L., Eisenstein, R. S. and Enns, C. A. (2002), Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE-expressing cells. J. Cell. Physiol., 190: 218–226. doi: 10.1002/jcp.10056
- Issue published online: 4 JAN 2002
- Article first published online: 14 DEC 2001
- Manuscript Accepted: 7 SEP 2001
- Manuscript Received: 9 JUL 2001
- NIH. Grant Number: DK54488
- NIH. Grant Number: DK47219
- NIH, National Heart, Lung, and Blood Institute (Training Program in Molecular Hematology). Grant Number: T32-HL00781
- USDA. Grant Number: 96-35200-3273
Iron regulatory proteins (IRPs), the cytosolic proteins involved in the maintenance of cellular iron homeostasis, bind to stem loop structures found in the mRNA of key proteins involved iron uptake, storage, and metabolism and regulate the expression of these proteins in response to changes in cellular iron needs. We have shown previously that HFE-expressing fWTHFE/tTA HeLa cells have slightly increased transferrin receptor levels and dramatically reduced ferritin levels when compared to the same clonal cell line without HFE (Gross et al., 1998, J Biol Chem 273:22068-22074). While HFE does not alter transferrin receptor trafficking or non-transferrin mediated iron uptake, it does specifically reduce 55Fe uptake from transferrin (Roy et al., 1999, J Biol Chem 274:9022–9028). In this report, we show that IRP RNA binding activity is increased by up to 5-fold in HFE-expressing cells through the activation of both IRP isoforms. Calcein measurements show a 45% decrease in the intracellular labile iron pool in HFE-expressing cells, which is in keeping with the IRP activation. These results all point to the direct effect of the interaction of HFE with transferrin receptor in lowering the intracellular labile iron pool and establishing a new set point for iron regulation within the cell. J. Cell. Physiol. 190: 218–226, 2002. © 2002 Wiley-Liss, Inc.