TCF25は,グルコースの飢餓下でリソソーム酸性化を強化することによって,代謝適応と細胞死をオーケストラする栄養センサとして機能する

Wenqing Ren¹, Hui Jiang², Qianqian Song²

¹Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.

Cell reports

|August 22, 2025

まとめ

転写因子25 (TCF25) は,リゾソームの活性を制御することによって,栄養ストレス中の細胞死を調節する. TCF25を阻害すると,細胞死や臓器損傷から保護され,治療の可能性が生まれます.

科学分野:

細胞生物学
メタボリズム
分子生物学

背景:

細胞は代謝経路の変化によって栄養の制限に適応します
栄養ストレスが長期間続くと細胞死亡が起こりますが制御メカニズムは不明です

研究の目的:

グルコース飢餓による細胞死の主な調節因子を特定する.
栄養ストレスに対する細胞反応におけるトランスクリプション・ファクター25 (TCF25) の役割を解明する.

主な方法:

ゲノム全体のCRISPR-Cas9スクリーニングで遺伝子レギュレータを特定します
グルコースの飢餓によるリソソーム経路の遺伝子濃縮の分析
細胞代謝と細胞死におけるTCF25機能の調査

主要な成果:

スクリーンでは,グルコース飢餓に関与するリソソーム経路遺伝子を特定しました.
TCF25はリソソーム酸性化とV-ATPaseによるATP生成を強化する.
長期にわたる飢餓はTCF25媒介のフェリチノファギーを活性化し,リソソーム膜の透過性を高め,細胞死を引き起こす.
TCF25またはV-ATPaseのノックアウトは細胞死を防ぐことができます.
TCF25欠乏症はマウスを肝臓不血症再注射による損傷から保護する.

結論:

TCF25はリソソーム機能を調節する重要な栄養センサとして機能します.
TCF25は,栄養ストレス下での適応反応 (オートファジー) と細胞死 (フェリチノファジー,LDCD) の両方を調節する.
TCF25の阻害は,代謝性および缺血性疾患に対する潜在的な治療戦略です.

キーワード:

CP: 細胞生物学 CP: 代謝 TCF25 について細胞死グルコース飢餓リソソーム代謝適応

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