Bcl-xLはミトコンドリアの膜ポテンシャルと体積ホメオスタシスを調節する

M G Vander Heiden¹, N S Chandel, E K Williamson

¹Gwen Knapp Center and Committee on Immunology, Department of Medicine, University of Chicago, Illinois 60637, USA.

Cell

|December 11, 1997

まとめ

腫れや外膜破裂を含むミトコンドリア機能障害は,細胞死で起こります. タンパク質Bcl-xLは,これらのミトコンドリアの変化を防止し,細胞の生存を促進します.

科学分野:

細胞生物学細胞生物学
バイオケミストリーバイオケミストリー
ミトコンドリアの研究

背景:

アポトーシスとネクロシスは,ミトコンドリアの生理学を乱します.
ミトコンドリアの完全性は,細胞の生存に不可欠です.
特定の刺激はミトコンドリアの腫れと膜破裂を引き起こします.

研究の目的:

ミトコンドリア膜タンパク質Bcl-xLが細胞死中のミトコンドリア恒常性を調節する役割を調査する.
Bcl-xLが,アポプトティックおよびネクロティック刺激によって誘発されたミトコンドリアの腫れや破裂を抑制できるかどうかを判断する.

主な方法:

細胞を様々なアポプトティックおよびネクロティック刺激で治療する.
ミトコンドリアの形態と膜の完全性の観察.
ミトコンドリア膜ポテンシャルの測定.
サイトクロームc放出の評価.

主要な成果:

さまざまなアポプトティックおよびネクロティック刺激により,進行的なミトコンドリアの腫れと外膜の破裂が誘発されました.
外部ミトコンドリア膜の破裂は,シトクロームcの放出と内部のミトコンドリア膜の脱極化につながった.
Bcl-xLは,アポプトティック刺激で治療された細胞におけるこれらのミトコンドリアの変化を抑制した.
Bcl-xLを発現する細胞は,ストレス下ではミトコンドリア膜の潜在能力を低下させ続けていた.
Bcl-xLは,酸化リン酸化を阻害する薬剤によって誘発されたミトコンドリアの腫れを予防しました.

結論:

Bcl-xLは,ミトコンドリア・ホメオスタシスの維持に重要な役割を果たします.
Bcl-xLは,ミトコンドリアの電気とオスモスのバランスを調節することによって,細胞生存を促進します.
Bcl-xLをターゲットにすることは,ミトコンドリア機能不全を含む状態のための治療戦略を提供することができます.

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