ミトコンドリア-リソソーム接触は,RAB7 GTP水解によってミトコンドリア分裂を調節する

Yvette C Wong¹, Daniel Ysselstein¹, Dimitri Krainc¹

¹Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

Nature

|January 25, 2018

まとめ

ミトコンドリアとライソソームは膜の接触部位でダイナミックに相互作用し細胞の健康に不可欠ですこの研究はこれらの接触が臓器動態を調節し病気に影響を及ぼすことを明らかにしています

科学分野:

細胞生物学
分子生物学
臓器生物学

背景:

ミトコンドリアとライソソームは細胞の恒常性のために不可欠であり,その機能不全は様々な病気に関連しています.
ミトコンドリアはネットワーク維持のためにダイナミックな分裂と融合を示し,細胞代謝に影響を与えます.
ライソソームはRAB7 GTPaseによって動的に調節され,活性状態と非活性状態の間をサイクルします.

研究の目的:

ミトコンドリア-リソソーム膜接触部位の形成と調節を特定し,特徴づけること.
これらの接触を調節するRAB7 GTPaseとTBC1D15の役割を明らかにする.
ミトコンドリア-リソソームの接触が,臓器動態と細胞ホメオスタシスに及ぼす機能的影響を理解する.

主な方法:

超構造分析のための電子顕微鏡
高解像度可視化のための構造化照明顕微鏡とコンフォーカル生細胞イメージング.
GTPaseの活性とタンパク質の徴集を研究する生化学的測定法

主要な成果:

ミトコンドリア-リソソームの接触は,健康な細胞でダイナミックに形成され,ミトファジーとは異なります.
アクティブでGTPに結合したRAB7は接触形成を促進し,ミトコンドリアへのTBC1D15の誘導は接触放出を媒介する.
リソソーム接触はミトコンドリア分裂を調節し,ミトコンドリア接触はリソソームRAB7水解を調節する.

結論:

ミトコンドリア-リソソームの接触は,ミトコンドリアとリソソームのダイナミクスの双方向的な調節を可能にします.
これらのコンタクトは細胞のホメオスタシスの維持に重要な役割を果たします
これらのコンタクトの調節不良は,ミトコンドリアおよびリソソーム機能障害を含む疾患の病理生理学に寄与する可能性があります.

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