Cytosolic aconitase and ferritin are regulated by iron in Caenorhabditis elegans.
Iron regulatory protein-1 (IRP-1) is a cytosolic RNA-binding protein that is a regulator of iron homeostasis in mammalian cells. IRP-1 binds to RNA structures, known as iron-responsive elements, located in the untranslated regions of specific mRNAs, and it regulates the translation or stability of these mRNAs. Iron regulates IRP-1 activity by converting it from an RNA-binding apoprotein into a [4Fe-4S] cluster protein exhibiting aconitase activity. IRP-1 is widely found in prokaryotes and eukaryotes. Here, we report the biochemical characterization and regulation of an IRP-1 homolog in Caenorhabditis elegans (GEI-22/ACO-1). GEI-22/ACO-1 is expressed in the cytosol of cells of the hypodermis and the intestine. Like mammalian IRP-1/aconitases, GEI-22/ACO-1 exhibits aconitase activity and is post-translationally regulated by iron. Although GEI-22/ACO-1 shares striking resemblance to mammalian IRP-1, it fails to bind RNA. This is consistent with the lack of iron-responsive elements in the C. elegans ferritin genes, ftn-1 and ftn-2. While mammalian ferritin H and L mRNAs are translationally regulated by iron, the amounts of C. elegans ftn-1 and ftn-2 mRNAs are increased by iron and decreased by iron chelation. Excess iron did not significantly alter worm development but did shorten their life span. These studies indicated that iron homeostasis in C. elegans shares some similarities with those of vertebrates.
Gourley
Brett L
BL
Eccles Program in Human Molecular Biology and Genetics and Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, Utah 84112, USA.
Parker
Samuel B
SB
Jones
Barbara J
BJ
Zumbrennen
Kimberly B
KB
Leibold
Elizabeth A
EA
D000154:Aconitate Hydratase / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003600:Cytosol / Q000201:enzymology; D017931:DNA Primers; D003676:Deferoxamine / Q000494:pharmacology*; D005293:Ferritins / Q000235:genetics*; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D017930:Genes, Reporter; D006801:Humans; D035941:Iron Regulatory Protein 1 / Q000737:chemistry / Q000235:genetics*; D007668:Kidney; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D005293:Ferritins; D000154:Aconitate Hydratase; D035941:Iron Regulatory Protein 1; D003676:Deferoxamine