シルカディアンクロック NAD+サイクルがミトコンドリアの酸化代謝を誘導する
Clara Bien Peek1, Alison H Affinati, Kathryn Moynihan Ramsey
1Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
まとめ
日常時計は,ニコチナミドアデニン・ディヌクレオチド (NAD(+)) レベルを制御することによって,毎日の代謝リズムを調節します. これはミトコンドリア機能とエネルギー生産に影響を与え,代謝を食事と断食サイクルと同期させます.
科学分野:
- バイオケミストリー バイオケミストリー
- 細胞生物学 細胞生物学
- メタボリズムは
背景:
- シルカディアン時計は,生理学的プロセスを24時間の光暗サイクルと同期する内生性振動器です.
- 酸化と還元細胞循環は,エネルギー代謝に不可欠です.
- ミトコンドリアの機能は,細胞のエネルギー生産に不可欠です.
研究 の 目的:
- NAD (((+)) 生合成とミトコンドリアの酸化機能の調節における昼夜時計の役割を調査する.
- 昼夜リズムと代謝経路を結びつける分子メカニズムを解明する.
- 生物学的利用可能性のNADのサーカディアン制御が生物の代謝にどのように影響するかを決定する.
主な方法:
- 昼間の転写フィードバックループの分析.
- ニコチナミドアデニンジヌクレオチド (NAD(+)) バイオシンセシスとアデノシントリホスファート (ATP) 生産の測定.
- ミトコンドリアタンパク質アセチル化と呼吸の評価.
- 孤立したミトコンドリアと昼間突然変異のマウスの研究.
- NAD (((+) サプリメントの実験.
主要な成果:
- 昼間の時計は,周期的なNADの生物合成,ATPの生成,ミトコンドリアの呼吸を調節する.
- ミトコンドリアのタンパク質アセチル化のサーカディアン調節により,酸化代謝が食事と断食のサイクルと同期されます.
- NAD (((+) 依存型脱酸化酵素サーチューイン3 (SIRT3) の循環制御は,酵素活性とミトコンドリア呼吸のリズムを制御する.
- NAD (((+) サプリメントは,変異したマウスの脱酸化を回復し,酸素消費を増加させた.
結論:
- シルカディアンクロックは,細胞の酸化代謝を毎日の食事と断食パターンと同期させます.
- NAD (((+) 生物利用性の循環制御は,ミトコンドリアの酸化機能を調節する重要なメカニズムです.
- この調節は,昼間のサイクル全体を通して,生物の代謝に影響を与えます.
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