The machinery of mitochondrial DNA maintenance : Novel components from a genome-wide RNAi screen
| Autor: | Fukuoh, Atsushi |
|---|---|
| Jazyk: | japonština |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | 純真学園大学雑誌. (4):55-63 |
| ISSN: | 2186-6481 |
| Popis: | application/pdf 要旨 : ミトコンドリアDNAの健全な複製, 修復そして伝達は生命にとって必要不可欠である. これらmtDNA維持機構に働く因子の異常は様々な病態と関連しているため, 長年興味深い研究対象となっているにもかかわらず, まだその全貌は明らかになっていない. 最近, 我々はキイロショウジョウバエS2細胞を用いてmtDNAの量的維持に着目したゲノムワイドRNAiスクリーニングを行い約100の陽性遺伝子を抽出することに成功した. 得られた陽性遺伝子群にはミトコンドリアDNAポリメラーゼなどの既知の因子に加えて, これまでmtDNAの維持との関連が予想されていなかった因子も多く得られた. 本稿ではスクリーニングで得られた新規因子の役割についてこれまでのmtDNA維持機構研究の成果とともに概説する. The faithful replication, repair and transmission of mitochondrial DNA (mtDNA) are essential for life. The machinery of mtDNA maintenance is only partially characterized despite the wide interest due to its involvement in disease, ranging from neurodegenerative disorders such as Parkinson’s disease through to susceptibility to cardiac ischemia, and perhaps aging. To identify novel components of this machinery, we performed a genome-wide RNAi screen in Drosophila S2 cells, assaying for loss of fluorescence of mtDNA nucleoids stained with the DNA-intercalating agent PicoGreen. In addition to previously characterized components of the mtDNA maintenance machineries, positive genes included many proteins of the cytosolic proteasome and ribosome, three proteins involved in vesicle transport, some other factors involved in mitochondrial biogenesis or nuclear gene expression, >30 mainly uncharacterized proteins and most subunits of ATP synthase. In this review, current understandings of the mtDNA maintenance including novel components from the screen are discussed. |
| Databáze: | OpenAIRE |
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