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ミトコンドリアのユビキノール酸化は,腫瘍の成長に必要である
Inmaculada Martínez-Reyes1, Luzivette Robles Cardona1, Hyewon Kong1
1Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Nature
|July 10, 2020
まとめ
腫瘍の成長には,トリカルボキシル酸 (TCA) サイクルとピリミジン合成を推進するウビキノールを酸化するために,ミトコンドリアの電子輸送鎖 (ETC) が必要です. このプロセスは in vivo の癌細胞増殖に不可欠です.
科学分野:
- 生物化学
- 癌 生物学
- ミトコンドリア生物学
背景:
- ミトコンドリアの電子輸送鎖 (ETC) は腫瘍の成長とATP生成に不可欠です.
- in vivo 腫瘍の進行を支える機能的ETCの正確な役割は不明である.
- ミトコンドリアはヒトの脳と肺腫瘍におけるグルコース酸化に不可欠です.
研究 の 目的:
- ETC が腫瘍の成長を支える特定のメカニズムを解明する.
- 癌の進行におけるユビキノン代謝とその下流経路の必要性を調査する.
- ETC複合体IIIが存在しない場合,NAD+再生だけでは腫瘍の成長に十分かどうかを判断する.
主な方法:
- ミトコンドリア複合体IIIに欠陥のあるがん細胞系を生成する.
- シオナ・インテスティナリスの代替オキシダゼ (AOX) を使って複合体III欠乏症を救済する.
- 複合体I,II,またはジヒドロロ酸脱水素酶 (DHODH) の欠陥を持つAOX発現細胞の腫瘍増殖を評価する.
- NAD+を再生するためにLactobacillus brevis NADH酸化酵素 (LbNOX) を発現する細胞における腫瘍の成長を評価する.
主要な成果:
- ミトコンドリア複合体IIIが欠けていたがん細胞は,腫瘍の成長に障害を示した.
- 腫瘍の成長はAOX発現によって回復し,ユビキノンの役割を強調した.
- I,II,またはDHODH複合体の喪失は,AOX発現細胞の腫瘍の成長を減少させた.
- LbNOXによるNAD+再生は,複合III欠乏細胞の腫瘍増殖を助長しなかった.
結論:
- 腫瘍の成長には,ユビキノールの酸化におけるETCの機能が必要である.
- ウビキノンの酸化は酸化トリカルボキシル酸サイクルとDHODHの活性を促進するために不可欠です.
- NAD+の再生は,体内で腫瘍の成長を支えるには不十分であり,ユビキノン代謝は非常に重要です.
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