エンドプラズマ網膜Ca2+のBAXとBAKの調節:アポトーシスのコントロールポイント
Luca Scorrano1, Scott A Oakes, Joseph T Opferman
1Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Department of Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA.
まとめ
プロアポプトティックタンパク質BAXとBAKは,エンドプラズマ網膜 (ER) とミトコンドリアのカルシウムレベルを調節することによって,アポトーシスの開始に不可欠です. その存在は,特定の細胞死経路に不可欠である.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- BAXとBAKは,ミトコンドリア機能障害の開始に関与する主要なプロアポプト性タンパク質です.
- これらのタンパク質は,エンドプラズマ網膜 (ER) にも局所化し,ミトコンドリアを超えた役割を示唆しています.
研究 の 目的:
- ERカルシウムホメオスタシスの調節におけるBAXとBAKの役割とそのアポトーシスへの影響について調査する.
- BAXとBAKの局所化は,異なるアポプトシス刺激に対する感受性にどのように影響するかを決定する.
主な方法:
- BAXとBAK (DKO細胞) が欠けているマウスの胚性線維芽細胞を使用した.
- 評価されたERカルシウム濃度 ([Ca2+]er) とミトコンドリアカルシウム吸収.
- カルシウム不調を正すためにSERCA発現を回復した.
- 細胞内貯蔵物からカルシウムを放出する物質やBH3のみの信号を含む様々な剤を用いてアポトーシス誘導を調査した.
- アポトーシスのERカルシウム放出とミトコンドリアBAX/BAKの必要性を調べました.
主要な成果:
- DKO細胞は,休息時の[Ca2+]erが減少し,ミトコンドリアのカルシウム吸収が低下した.
- SERCA発現は[Ca2+]erとミトコンドリアカルシウム吸収を回復し,DKO細胞を特定のアポプトシス刺激に再感知させました.
- ミトコンドリアにBAXを標的にすることで,アポトーシスはBH3のみの信号にのみ回復しました.
- 多くの固有のアポプトシス信号は,ERカルシウム放出とミトコンドリアのBAX/BAKの両方を必要とした.
結論:
- BAXとBAKは,ERとミトコンドリアの両方で特定のアポプトティック信号のための重要なゲートウェイとして機能します.
- BAXとBAKによるERカルシウム調節は,特定の細胞ストレスに対する反応としてアポトーシスの開始に不可欠です.
- BAXとBAKの局所化は,異なるアポプトシス経路を媒介する彼らの役割を決定する.
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