ミトコンドリアのストレスシグナルとプロテオスタシスの神経内分泌調整
Kristen M Berendzen1, Jenni Durieux1, Li-Wa Shao2
1The Glenn Center for Aging Research, Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell
|September 10, 2016
まとめ
神経退行性疾患は 広範な代謝変化を引き起こします この研究では セロトニンによって伝達される ニューロンのストレスシグナルが ミトコンドリアの反応を誘発し 動物全体の生理に影響を及ぼします
科学分野:
- 神経生物学
- 細胞生物学
- 代謝の調節
背景:
- 神経変性疾患には 毒性タンパク質の蓄積と 組織的な代謝変化が含まれます
- 中枢神経系のストレスと周辺の代謝変化を結びつけるメカニズムは不明である.
- 神経細胞におけるタンパク質毒性ストレスが,内分泌信号を通じた全身反応を誘発する可能性があります.
研究 の 目的:
- タンパク質毒性疾患中のミトコンドリア・ホメオスタシスの調節におけるニューロンストレスの役割を調査する.
- 神経細胞のプロテオ毒性に対する全身反応に関与するシグナル伝達経路を解明する.
主な方法:
- タンパク質の集積と神経のストレスを研究するためのモデル生物としてC.elegansを使用した.
- 結合傾向のあるタンパク質とミトコンドリアの相互作用を研究した.
- ミトコンドリアの展開タンパク質応答 (UPR) の誘導を評価した.
- 信号伝達における濃厚なコア膀の放出とセロトニンの分泌の役割を調べた.
主要な成果:
- ニューロンの結合傾向のあるタンパク質がミトコンドリアに結合し,グローバル UPR を誘発します.
- このミトコンドリア反応は 動物全体の生理に影響します
- セロトニンの分泌はストレス信号の伝播に不可欠です.
- この発見は 栄養素感知ネットワークが 臓器間のコミュニケーションに 協力していることを示唆しています
結論:
- ニューロンのプロテオキシカル・ストレスは,UPRによって全身の代謝変化を引き起こします.
- セロトニン媒介のシグナル伝達は,神経細胞からのミトコンドリアストレス伝達に不可欠です.
- このメカニズムは タンパク質の折り畳みストレスへの反応として 細胞間通信の新たな経路を示しています
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