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SIRT3は,リバーシブルな酵素脱酸化によってミトコンドリア脂肪酸の酸化を調節する
Matthew D Hirschey1, Tadahiro Shimazu, Eric Goetzman
1Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA.
Nature
|March 6, 2010
まとめ
Sirtuin 3 (SIRT3) が欠けているマウスは,LCADのような重要な酵素の過酸化により,断食中に脂肪酸酸化が低下し,代謝機能障害を引き起こす. これはSIRT3を強調しています.
科学分野:
- ミトコンドリアの生物学と代謝
- 酵素の調節と翻訳後の変化
背景:
- サーチューインは,ストレス反応と代謝適応に関与するNAD (((+)) 依存型脱酸化酵素である.
- Sirtuin 3 (SIRT3) は,代謝酵素アセチレーションを調節するミトコンドリアの脱セチラゼです.
- SIRT3が欠けているマウスは,基礎条件下ではミトコンドリアタンパク質のハイパーアセチル化を示す.
研究 の 目的:
- 断食中のミトコンドリア脂肪酸酸化を調節するSIRT3の役割を調査する.
- 禁食への代謝適応に関与する特定のSIRT3標的を特定する.
主な方法:
- 禁食中の野生型およびSIRT3欠乏マウスからの肝臓と茶色の脂肪組織の比較分析.
- 脂肪酸酸化中間物質とトリグリセリドの測定.
- LCADを含むハイパーアセチル化ミトコンドリアタンパク質を特定するための質量スペクトロメトリ.
- SIRT3.3を用いたインビトロおよびインビボ脱エチル化アッセイ.
主要な成果:
- 断食中のSIRT3発現は,肝臓と茶色の脂肪組織で上調される.
- SIRT3欠乏症のマウスは,断食中のライシン42で脂肪酸酸化が低下し,トリグリセリドが増加し,LCADの過酸化を示しています.
- LCADのハイパーアセチル化により,酵素活性が低下する.
- SIRT3欠乏したマウスは,減量のATPと冷たい不耐性を含む,断食誘発脂肪酸酸化障害の特徴を示します.
結論:
- アセチル化は,ミトコンドリア脂肪酸酸化のための新しい調節メカニズムです.
- SIRT3は,ミトコンドリアの中間代謝と断食中の脂肪酸の利用を調節する上で重要な役割を果たします.
- SIRT3媒介によるLCADの脱エチル化は,断食中の代謝ホメオスタシスの維持に不可欠です.
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