Iron differentially stimulates translation of mitochondrial aconitase and ferritin mRNAs in mammalian cells. Implications for iron regulatory proteins as regulators of mitochondrial citrate utilization - PubMed (original) (raw)
. 1998 Feb 6;273(6):3740-6.
doi: 10.1074/jbc.273.6.3740.
Affiliations
- PMID: 9452506
- DOI: 10.1074/jbc.273.6.3740
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Iron differentially stimulates translation of mitochondrial aconitase and ferritin mRNAs in mammalian cells. Implications for iron regulatory proteins as regulators of mitochondrial citrate utilization
K L Schalinske et al. J Biol Chem. 1998.
Free article
Abstract
Utilization of mRNAs containing iron-responsive elements (IREs) is modulated by iron-regulated RNA-binding proteins (iron regulatory proteins). We examine herein whether iron differentially affects translation of ferritin and mitochondrial aconitase (m-Acon) mRNAs because they contain a similar but not identical IRE in their 5'-untranslated regions. First, we demonstrate that m-Acon synthesis is iron-regulated in mammalian cells. In HL-60 cells, hemin (an iron source) stimulated m-Acon synthesis 3-fold after 4 h compared with cells treated with an iron chelator (Desferal). Furthermore, hemin stimulated m-Acon synthesis 2-4-fold in several cell lines. Second, we show that iron modulates the polysomal association of m-Acon mRNA. We observed m-Acon mRNA in both ribonucleoprotein and polyribosomal fractions of HL-60 cells. Hemin significantly increased the polyribosomal association and decreased the ribonucleoprotein abundance of m-Acon mRNA in HL-60 cells. Third, our results indicate that iron differentially regulates translation of m-Acon and ferritin mRNAs. A dose response to hemin in HL-60 cells elicited a 2-2.4-fold increase in m-Acon synthesis within 5 h compared with untreated cells, whereas ferritin synthesis was stimulated 20-100-fold. We conclude that iron modulates m-Acon synthesis at the translational level and that iron regulatory proteins appear to differentially affect translation of IRE-containing mRNAs.
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