ピューリノソームとミトコンドリアの空間的コロカライゼーションと機能的リンク
Jarrod B French1, Sara A Jones2, Huayun Deng3
1Department of Biochemistry and Cell Biology, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA. jarrod.french@stonybrook.edu fangy2@corning.com zhuang@chemistry.harvard.edu sjb1@psu.edu.
Science (New York, N.Y.)
|February 26, 2016
まとめ
ピューリン生物合成酵素は,ミトコンドリアと結合したピューリノソームを形成する. ラパミシン (mTOR) シグナリングのメカニスティックターゲットは,この相互作用を調節し,ピューリノソームの組み立てとヌクレオチド代謝を制御します.
科学分野:
- 細胞生物学
- 生物化学
- 分子生物学
背景:
- ピューリノソームは,ピューリン生物合成酵素によって形成される動的細胞構造である.
- ピューリノソームの形成と機能の空間時間的調節は,ほとんど特徴づけられていない.
研究 の 目的:
- ピューリノソームとミトコンドリアの関係を調べる
- プーリノソームの組み立てを制御する細胞内信号伝達経路を特定する.
主な方法:
- ピューリノソーム-ミトコンドリアのコロカライゼーションを視覚化するための超高解像度顕微鏡.
- ミトコンドリアで purinome酵素を分離するための細胞分化.
- シグナルレギュレータを特定するために,ラベルフリーアッセイを用いたキノームスクリーニング.
- ラパミシン (mTOR) のメカニズム的標的の薬理学的抑制
主要な成果:
- ピューリノソームはミトコンドリアとコロカライズすることが判明した.
- ピューリノソーム形成はミトコンドリア機能と代謝によって調節された.
- ラパミシン (mTOR) シグナリングのメカニスティックターゲットは,ピューリノソームアセンブリの重要なレギュレータとして特定されました.
- mTORの抑制により, purinosom- mitochondriaのコロカライゼーションが妨げられ, purinosomの形成が抑制された.
結論:
- ピューリノソームとミトコンドリアの間には,mTORシグナル伝達によってリンクが存在する.
- mTORは,ピュリノソーム形成の空間時間的な制御において重要な役割を果たします.
- mTORは, purin生物合成酵素の空間的組織を通して,核酸代謝を調節する.
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