PUBLICATION
Overexpression of Drosophila mitoferrin in l(2)mbn cells results in dysregulation of Fer1HCH expression
- Authors
- Metzendorf, C., Wu, W., and Lind, M.I.
- ID
- ZDB-PUB-090526-21
- Date
- 2009
- Source
- The Biochemical journal 421(3): 463-471 (Journal)
- Registered Authors
- Keywords
- Iron homeostasis, mitochondrial iron metabolism, iron transport, Drosophila
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Apoferritins/chemistry
- Apoferritins/genetics*
- Apoferritins/metabolism
- Cell Line
- Drosophila Proteins/chemistry
- Drosophila Proteins/genetics*
- Drosophila Proteins/metabolism
- Drosophila melanogaster/chemistry
- Drosophila melanogaster/genetics*
- Drosophila melanogaster/metabolism
- Gene Expression Regulation
- Iron/metabolism
- Iron-Regulatory Proteins/genetics
- Iron-Regulatory Proteins/metabolism
- Iron-Sulfur Proteins/genetics
- Iron-Sulfur Proteins/metabolism
- Molecular Sequence Data
- Sequence Alignment
- Up-Regulation*
- PubMed
- 19453295 Full text @ Biochem. J.
Citation
Metzendorf, C., Wu, W., and Lind, M.I. (2009) Overexpression of Drosophila mitoferrin in l(2)mbn cells results in dysregulation of Fer1HCH expression. The Biochemical journal. 421(3):463-471.
Abstract
Mrs3p and Mrs4p (Mrs3/4p) are mitochondrial iron carrier proteins that play important roles in iron-sulphur cluster (ISC) 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. Little is known about the ubiquitously expressed paralogue mfrn2. We identified only one mitoferrin gene (dmfrn) in the genome of Drosophila melanogaster; moste likely an orthologue of mfrn2. Overexpression of dmfrn in the Drosophila l(2)mbn cell line (mbn-dmfrn) resulted in decreased IRP-1A/IRE binding activity, increased cytoplasmic aconitase activity and slightly decreased iron content when compared to control cell lines, whereas iron loading resulted in decreased IRP1-A/IRE binding, and increased cellular iron content of similar levels in all cell lines. At iron loading conditions cytoplasmic aconitase activity was increased in all cell lines, with slightly higher activity 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 to control cell lines mbn-dmfrn cells had higher Fer1HCH 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 is likely to depend on cytoplasmic ISC protein maturation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping