レドックス依存型チャペロンによる誤折りタンパク質の寿命制御
Sarah Hanzén1, Katarina Vielfort1, Junsheng Yang2
1Department of Chemistry and Molecular Biology (CMB), University of Gothenburg, Medicinaregatan 9C, 413 90 Göteborg, Sweden; Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 7A, 413 90 Göteborg, Sweden.
Cell
|June 7, 2016
まとめ
酵母ペロキシレドキシン (Tsa1) の量を増やすと,カロリー制限とは無関係に寿命が延びる. これはHsp70とTsa1を伴うものです.
科学分野:
- 細胞生物学
- 老化に関する研究
- 生物化学
背景:
- カロリー制限 (CR) は様々な生物の寿命を延ばすことで知られています.
- CRは,過酸化水素 (H2O2) を取り除く過酸化水素 (Prxs) の年齢関連の酸化を抑制する.
- 特定のPRXと老化におけるその調節の役割は完全に理解されていません.
研究 の 目的:
- 主要な酵母細胞性ペロキシレドキシンであるTsa1の寿命延長における役割を調査する.
- Tsa1が寿命に影響するメカニズムを特定し,特にシャパロンと酸化ストレスとの関係を明らかにする.
主な方法:
- 酵母におけるTsa1の遺伝子操作
- 寿命,H2O2の除去,そしてゲノムの安定性を測定する.
- タンパク質の相互作用 (Tsa1 と Hsp70) を研究するための共免疫プレシピテーション
- タンパク質の集積と老化中のユビキチン化の分析
主要な成果:
- Tsa1の投与量の増加は,CRとは無関係で酵母の寿命を延ばし,Hsp70の伴侶に依存した.
- この寿命の延長には,H2O2の除去が増加したり,ゲノムの安定性が改善されたりしませんでした.
- Tsa1はHsp70と物理的に相互作用し,H2O2誘発のTsa1の高酸化は,老化中にHsp70とHsp104をタンパク質集積物に誘導するために重要である.
- Tsa1は,ユビキチン化アグレガートの蓄積を抑制し,硫黄素媒介による高酸化 Tsa1の減少は,アグレガートのクリアランスを助長した.
結論:
- Tsa1は,Hsp70チャペロンが介在する,プロテオスタシスと寿命制御における新しい役割を果たします.
- 水素過酸化物 (H2O2) のシグナル伝達は,老化中のタンパク質ホメオスタシス (プロテオスタシス) の調節に関与する.
- ペロキシレドキシンの可逆性高酸化は,真核生物の老化過程で選択的な利点を提供します.
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