mitochondrial Unfolded Protein Response は,レトロマー依存の Wnt シグナリングによって,細胞非自律的に媒介される
Qian Zhang1, Xueying Wu2, Peng Chen1
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, 100049 Beijing, China.
Cell
|July 31, 2018
まとめ
ミトコンドリアのストレス信号は Wnt信号を用いてニューロンから他の組織に伝わります この細胞非自律的なミトコンドリアの展開タンパク質反応 (UPRmt) はレトロマー複合体を含み,生物を保護する.
科学分野:
- 細胞生物学
- 神経科学
- 遺伝学
背景:
- ミトコンドリア機能障害は,ミトコンドリア展開タンパク質反応 (UPRmt) を引き起こす.
- この反応は細胞間非自律的に発生し,ストレス信号の細胞間通信を示します.
- これらの伝達経路を理解することは 生物の保護に不可欠です
研究 の 目的:
- 神経系から外周組織にミトコンドリアのストレス信号が伝播するメカニズムを調査する.
- 細胞間通信経路に関与する 分子プレーヤーを特定します
主な方法:
- モデル生物としてC.エレガンスを利用した.
- UPRmtにおけるレトロマー依存のWntシグナルの役割を調査した.
- ニューロンのミトコンドリアストレス (polyQ40,cco-1減少) が周辺のUPRmtに及ぼす影響を調べました.
- レトロマー複合体の変異 (MIG- 14) とWntリガンド (EGL- 20) 発現の影響を評価した.
主要な成果:
- ニューロンのミトコンドリアストレスは,Wnt依存の細胞非自律的なUPRmtを誘発する.
- Wnt分泌 (MIG-14経由) に不可欠なレトロマー複合体は,UPRmt信号を伝播するために必要である.
- WntリガンドEGL-20のニューロン発現は,細胞非自律的なUPRmtを誘発するのに十分である.
- このシグナル伝達経路は,レトロマー複合体の機能,Wntシグナル伝達,およびセロトニンに依存しています.
結論:
- Wnt信号は神経系から外周組織へのミトコンドリアのストレス信号の伝達のための重要な媒介として機能する.
- レトロマー複合体は,この細胞間通信を促進する Wnt リガンドの分泌に重要な役割を果たします.
- Wntシグナリングは"ミトキーン"シグナルの強力な候補として特定され,全身的なミトコンドリアの健康におけるその役割を強調しています.
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