ミトコンドリア翻訳には,葉酸依存型tRNAメチル化が必要です
Raphael J Morscher1,2, Gregory S Ducker1,2, Sophia Hsin-Jung Li3
1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Nature
|January 25, 2018
まとめ
ミトコンドリアの葉酸代謝,特にセリンヒドロキシメチルトランスフェラーゼ2 (SHMT2) は,ミトコンドリアのtRNAを改変するために重要である. このtRNAの改変は,酸化性リン酸化による正確なタンパク質合成と細胞のエネルギー生産に不可欠です.
科学分野:
- 生物化学
- 分子生物学
- 細胞の代謝
背景:
- 葉酸は 一酸化炭素の代謝に不可欠であり 生物合成の経路に不可欠です
- ミトコンドリアの葉酸酵素は増殖する細胞や癌で上位に調節されます.
- 細胞機能におけるミトコンドリア葉酸の正確な役割は完全に理解されていません.
研究 の 目的:
- 細胞機能におけるミトコンドリアの葉酸代謝の特定の役割を調査する.
- ミトコンドリアの葉酸酵素活性低下が細胞プロセスに与える影響を決定する.
- ミトコンドリアの葉酸がエネルギー代謝に影響を与えるメカニズムを解明する.
主な方法:
- セルリンヒドロキシメチルトランスフェラーゼ2 (SHMT2) 活性が欠けているヒト細胞を生成.
- トランスレーションを分析するためにミトコンドリアリボソームプロファイリングを使用した.
- 酸化リン酸化と呼吸連鎖酵素発現の評価
主要な成果:
- SHMT2の活性低下はミトコンドリア変換と酸化リン酸化を阻害する.
- SHMT2は5,10-メチレンテトラヒドロフォレートを生成し,tRNA改変のためのメチルドナー (タウリノメチルウリジン) を提供する.
- 欠陥のあるtRNA変異は特定のコドンでリボソームの停滞を引き起こし,呼吸酵素の発現を損なう.
結論:
- 哺乳類のミトコンドリアは,tRNAメチル化のために,葉酸由来の1炭素単位を使用する.
- このtRNAの改変は,正確なミトコンドリア翻訳と酸化リン酸化に不可欠です.
- 葉酸代謝やSHMT2機能の障害は細胞のエネルギー生産に悪影響を及ぼします.
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