論文 - 詳細
| RRC ID | 4303 |
|---|---|
| 著者 | Sugimoto T, Mori C, Takanami T, Sasagawa Y, Saito R, Ichiishi E, Higashitani A. |
| タイトル | Caenorhabditis elegans par2.1/mtssb-1 is essential for mitochondrial DNA replication and its defect causes comprehensive transcriptional alterations including a hypoxia response. |
| ジャーナル | Exp Cell Res |
| Abstract |
DNA polymerase gamma and mtSSB are key components of the mtDNA replication machinery. To study the biological influences of defects in mtDNA replication, we used RNAi to deplete the gene for a putative mtSSB, par2.1, in Caenorhabditis elegans. In previous systematic RNAi screens, downregulation of this gene has not caused any clearly defective phenotypes. Here, we continuously fed a dsRNA targeting par2.1 to C. elegans over generations. Seventy-nine percent of F1 progeny produced 60-72 h after feeding grew to adulthood but were completely sterile, with an arrest of germline cell proliferation. Analyses of mtDNA copy number and cell cytology indicated that the sterile hermaphrodites had fewer mitochondria. These results indicated that par2.1 essentially functions for germline cell proliferation through mtDNA replication; we therefore termed it mtssb-1. Comprehensive transcriptional alterations including hypoxia response induction dependent on and independent of hif-1 function, occurred by RNAi depletion of mtssb-1. Treatment with ethidium bromide, which impairs mtDNA replication and transcription, caused similar transcriptional alterations. In addition, the frequency of apoptosis in the germline cells was reduced in fertile progeny with a partial RNAi effect. These suggest that RNAi depletion of C. elegans mtssb-1 is useful as a model system of mitochondrial dysfunction. |
| 巻・号 | 314(1) |
| ページ | 103-14 |
| 公開日 | 2008-1-1 |
| DOI | 10.1016/j.yexcr.2007.08.015 |
| PII | S0014-4827(07)00398-9 |
| PMID | 17900564 |
| MeSH | Animals Apoptosis / genetics Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Cell Proliferation DNA Replication / genetics* DNA, Mitochondrial / genetics* DNA-Binding Proteins / genetics* Down-Regulation / genetics Germ-Line Mutation / genetics Hypoxia / genetics* Hypoxia / metabolism Hypoxia / physiopathology Hypoxia-Inducible Factor 1 / genetics Infertility / genetics Mitochondria / genetics RNA Interference Regulatory Elements, Transcriptional / genetics Xenopus Proteins / genetics |
| IF | 3.383 |
| 引用数 | 19 |
| WOS 分野 | ONCOLOGY CELL 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 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 | tm2685 |