ATG3とATG12の結合は,ミトコンドリア・ホメオスタシスと細胞死を調節する

Lilliana Radoshevich¹, Lyndsay Murrow, Nan Chen

¹Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA.

Cell

|August 21, 2010

まとめ

ATG12-ATG3複合体はミトコンドリア質量と細胞死を調節し,オートファギーの開始における機能を超えたATG12結合システムの新しい役割を明らかにします.

科学分野:

細胞生物学細胞生物学
分子生物学は分子生物学である.
オートファジー研究オートファジー研究

背景:

ATG12は,マクロオートファギーに不可欠なユビキチンのような変形剤です.
その既知の結合標的は,オートファギーの調節体であるATG5である.
ATG3は,オートファジー中のATG8/LC3脂化に不可欠なE2型の酵素です.

研究の目的:

ATG12結合のための新しい基質を特定する.
ATG3.3へのATG12結合の機能を調査する.
細胞プロセスにおけるATG12-ATG3複合体の役割を調査する.

主な方法:

ATG7をE1酵素として使用してATG3へのATG12結合を調査した.
ATG12-ATG3複合体の形成を妨害した結果,オートファギーの影響を分析した.
ミトコンドリア質量と細胞死経路の変化を評価した.

主要な成果:

ATG3をATG12結合の新しい基質として特定し,共振性ATG12-ATG3複合体を形成しました.
ATG3へのATG12結合の障害は,飢餓によって誘発されたオートファギーを損なうことはなかった.
ATG12-ATG3複合体の形成が欠如すると,ミトコンドリア質量が増加し,ミトコンドリア細胞死が抑制されます.

結論:

ATG12-ATG3結合システムは,初期のオートファギーのステップとは独立して,ミトコンドリアのホメオスタシスに役割を果たします.
この発見は,ATG12結合系がオートファゴソーム形成を超えた細胞機能に関与していることを示している.

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