脂質生物合成はミトコンドリアから細胞へのストレス反応を調整する

Hyun-Eui Kim¹, Ana Rodrigues Grant², Milos S Simic¹

¹Glenn Center for Research on Aging, 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

ミトコンドリアのストレスと代謝の変化は細胞タンパク質の品質管理システム間の通信を活性化しますアルツハイマー病やパーキンソン病のようなタンパク質の誤折り症に予防します

科学分野:

細胞生物学
神経科学
代謝疾患

背景:

ミトコンドリア機能不全は,年齢によって発症するタンパク質の誤折り症に関連しています.
細胞タンパク質のホメオスタシスは,ER,ミトコンドリア,細胞溶液における展開タンパク質応答 (UPR) に依存する.
これらのUPR間の交信はよくわかっていませんが細胞の回復力には不可欠です

研究の目的:

ミトコンドリアのタンパク質ホメオスタシスと細胞の折り畳みを結びつけるメカニズムを調査する.
代謝の変化が異なるUPR間のコミュニケーションにどのように影響するかを理解する.
タンパク質の誤折り症の潜在的治療標的を特定する.

主な方法:

ミトコンドリアと細胞塩分タンパク質のホメオスタシスを結びつける保存されたメカニズムを研究した.
ミトコンドリアのストレスや小分子活性化剤によって引き起こされる代謝の再構成を調査した.
分析された遺伝子発現の変化はミトコンドリアと細胞細胞のUPRによって調整される.

主要な成果:

リピッドホメオスタシスによるミトコンドリアと細胞タンパク質の折り畳みを結びつける強力なメカニズムを発見した.
代謝の変化は,ミトコンドリアと細胞細胞の両方のUPRによって調整された遺伝子発現を誘導する.
この協調的な反応は細胞を病気に関連したタンパク質から守ります

結論:

代謝状態によって調節される UPR の間で新しい通信システムが存在する.
この複雑なコミュニケーション経路はタンパク質の恒常性を維持するために不可欠です
この臓器間の通信ネットワークをターゲットにすると神経退行性疾患の新たな治療戦略が生まれます

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