論文 - 詳細
| RRC ID | 46097 |
|---|---|
| 著者 | González-Cabo P, Bolinches-Amorós A, Cabello J, Ros S, Moreno S, Baylis HA, Palau F, Vázquez-Manrique RP. |
| タイトル | Disruption of the ATP-binding cassette B7 (ABTM-1/ABCB7) induces oxidative stress and premature cell death in Caenorhabditis elegans. |
| ジャーナル | J Biol Chem |
| Abstract |
X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare inherited disorder characterized by mild anemia and ataxia. XLSA/A is caused by mutations in the ABCB7 gene, which encodes a member of the ATP-binding cassette transporter family. Studies in yeast, mammalian cells, and mice have shown that ABCB7 functions in the transport of iron-sulfur (Fe-S) clusters into the cytoplasm. To further investigate the mechanism of this disease, we have identified and characterized the Caenorhabditis elegans homologue of the ABCB7 gene, abtm-1. We have studied the function of abtm-1 using mutants and RNAi. abtm-1-depleted animals produce arrested embryos that have morphogenetic defects and unusual premature, putative apoptotic events. abtm-1(RNAi) animals also show accumulation of ferric iron and increased oxidative stress. Despite the increased level of oxidative stress in abtm-1(RNAi) animals, they have an increased life span. We observed accumulation of DAF-16/FOXO in the nuclei of affected animals and elevation of the expression of SOD-3, a well established target of DAF-16, which may explain the increased life span extension of these animals. abtm-1 is strongly expressed in tissues with a high energy demand, and abtm-1(RNAi) animals have phenotypes that reflect the need for abtm-1 in these tissues. Finally, we show that reducing the function of other genes involved in Fe-S cluster production produces similar phenotypic consequences to abtm-1 loss of function. Therefore, ablation of abtm-1 in C. elegans provides a model in which to investigate the mechanism underlying XLSA/A. |
| 巻・号 | 286(24) |
| ページ | 21304-14 |
| 公開日 | 2011-6-17 |
| DOI | 10.1074/jbc.M110.211201 |
| PII | S0021-9258(19)49012-1 |
| PMID | 21464130 |
| PMC | PMC3122190 |
| MeSH | ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism* ATP-Binding Cassette Transporters / physiology Animals Apoptosis Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Cell Death Cytoplasm / metabolism DNA, Complementary / metabolism Frataxin Gene Expression Regulation, Developmental* Iron / metabolism Iron-Binding Proteins / metabolism Mitochondria / metabolism Models, Biological Oxidative Stress* RNA Interference |
| IF | 4.238 |
| 引用数 | 21 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm2721 |