フーマレートは哺乳類の電子伝送鎖の末端受容体である
Jessica B Spinelli1,2, Paul C Rosen1,2,3, Hans-Georg Sprenger1,2
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Science (New York, N.Y.)
|December 2, 2021
まとめ
ミトコンドリアの電子輸送鎖 (ETC) の機能を維持するために,哺乳類は酸素が限られているとき,代替の電子受容体としてフーマレートを使用することができます. サクシネート脱水素酵素複合体のこの逆の機能は,低酸素状態での細胞呼吸を維持する.
科学分野:
- 生物化学
- 細胞呼吸
- ミトコンドリア機能
背景:
- ミトコンドリアの電子輸送鎖 (ETC) は通常,酸素を端末電子受容体 (TEA) として使用する.
- 細胞の呼吸とATPの生成は,ETCを通る連続した電子の流れに非常に依存しています.
- 酸素減少への障害はミトコンドリア機能の維持に重大な課題をもたらす.
研究 の 目的:
- 酸素減少が阻害されたとき,ミトコンドリアのETCにおける電子の流れの代替経路を調査する.
- 哺乳類の細胞における代替端末電子受容体を特定する.
- 低酸素状態でミトコンドリア機能を維持するメカニズムを理解する.
主な方法:
- 細胞モデルにおける酸素減少の抑制
- ETC内の電子の流れと代謝物のレベルを測定する.
- サクシネート脱水素酵素 (SDH) 複合体を含む酵素活性の分析
- 様々なマウス組織におけるTEAとしてのフマラートの役割の評価.
主要な成果:
- 複合体Iと二酸化オロ酸脱水素酶 (DHODH) は,酸素還元が阻害されている場合でも,電子をETCに積むことができます.
- 抑制された酸素還元下でユビキノールの蓄積は,SDH複合体を逆方向に駆動する.
- この逆のSDH活性により,電子がフーマラートに沈着し,DHODHとコンプレックスIを維持します.
- マウスの組織は,TEAとしてフーマレートを利用する様々な能力を発揮し,しばしば低酸素状態でSDHの活動を逆転させます.
結論:
- 哺乳類の細胞は,酸素が限られているときにTEAとしてフーマレートを利用するETCの電子フローの回路を持っています.
- SDH複合体の逆機能は,酸素不足下でミトコンドリア機能を維持するための重要なメカニズムである.
- この代替的な電子フロー経路は 細胞呼吸が低酸素環境への適応性を強調しています
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