NLRP3炎症体活性化におけるミトコンドリアの役割
Rongbin Zhou1, Amir S Yazdi, Philippe Menu
1Department of Biochemistry, Center of Immunity and Infection, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
Nature
|December 3, 2010
まとめ
炎症に不可欠なNLRP3炎症体は,損傷したミトコンドリアによって活性化されます. オートファギーの阻害はミトコンドリアの損傷を引き起こし,NLRP3炎症体の活性化と炎症性疾患につながる.
科学分野:
- 細胞生物学 細胞生物学
- 免疫学 免疫学とは
- ミトコンドリア生物学
背景:
- NLRP3炎症ゾームは,細胞の危険信号に対する炎症反応を媒介する.
- その調節には,未確認の臓器細胞からのオートファギーと活性酸素種 (ROS) が含まれる.
研究 の 目的:
- NLRP3炎症体活性化におけるミトコンドリアの役割を調査する.
- NLRP3炎症ゾームを調節するROSの源を特定するために.
主な方法:
- NLRP3炎症体活性化に対するミトファジー/オートファジー阻害の影響を研究した.
- 炎症体の活性化中にNLRP3とASCの局所化を調査した.
- ミトコンドリア機能障害 (VDAC阻害経由) がROS生成と炎症体活性化に及ぼす影響を調査した.
主要な成果:
- ミトファジー/オートファジー阻害により,損傷したROS生成ミトコンドリアが蓄積され,NLRP3炎症体が活性化しました.
- NLRP3とASCは周核空間に転位し,活性化するとERとミトコンドリアと同局化します.
- ミトコンドリアの活性抑制により,ROS生成とNLRP3炎症体活性化が抑制されました.
結論:
- NLRP3炎症ゾームは,ミトコンドリア機能不全を感知する.
- ミトコンドリアの損傷は炎症性疾患に寄与する.
- この研究は,ミトコンドリアをNLRP3炎症体活性を調節するROSの源として特定しています.
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