| 19453295 |
Metzendorf C, Wu W, Lind MI: Overexpression of Drosophila mitoferrin in l (2) mbn cells results in dysregulation of Fer1HCH expression. Biochem J. 2009 Jul 15;421(3):463-71.
Mrs3p and Mrs4p (Mrs3/4p) are yeast mitochondrial iron carrier proteins that play important roles in ISC (iron-sulphur cluster) and haem biosynthesis. At low iron conditions, mitochondrial and cytoplasmic ISC protein maturation is correlated with MRS3/4 expression. Zebrafish mitoferrin1 (mfrn1), one of two MRS3/4 orthologues, is essential for erythropoiesis, but little is known about the ubiquitously expressed paralogue mfrn2. In the present study we identified a single mitoferrin gene (dmfrn) in the genome of Drosophila melanogaster, which is probably an orthologue of mfrn2. Overexpression of dmfrn in the Drosophila l (2) mbn cell line (mbn-dmfrn) resulted in decreased binding between IRP-1A (iron regulatory protein 1A) and stem-loop RNA structures referred to as IREs (iron responsive elements). mbn-dmfrn cell lines also had increased cytoplasmic aconitase activity and slightly decreased iron content. In contrast, iron loading results in decreased IRP-1A-IRE binding, but increased cellular iron content, in experimental mbn-dmfrn and control cell lines. Iron loading also increases cytoplasmic aconitase activity in all cell lines, but with slightly higher activity observed in mbn-dmfrn cells. From this we concluded that dmfrn overexpression stimulates cytoplasmic ISC protein maturation, as has been reported for MRS3/4 overexpression. Compared with control cell lines, mbn-dmfrn cells had higher Fer1HCH (ferritin 1 heavy chain homologue) transcript and protein levels. RNA interference of the putative Drosophila orthologue of human ABCB7, a mitochondrial transporter involved in cytoplasmic ISC protein maturation, restored Fer1HCH transcript levels of iron-treated mbn-dmfrn cells to those of control cells grown in normal medium. These results suggest that dmfrn overexpression in l (2) mbn cells causes an 'overestimation' of the cellular iron content, and that regulation of Fer1HCH transcript abundance probably depends on cytoplasmic ISC protein maturation. |
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