生物
先天免疫系统
细胞生物学
溶解循环
线粒体
程序性细胞死亡
氧化应激
信号转导
细胞骨架
免疫系统
细胞
氧化磷酸化
细胞凋亡
PI3K/AKT/mTOR通路
代谢途径
内源性凋亡
细胞代谢
经典补体途径
细胞膜
细胞信号
粒体自噬
免疫学
半胱氨酸蛋白酶
获得性免疫系统
板层
活性氧
mTORC2型
线粒体内膜
TOR信号
作者
Yaqiu Wang,Jianlin Lu,Alexandre F. Carisey,Sangappa B. Chadchan,Ha Won Lee,R. K. Subbarao Malireddi,Bhesh Raj Sharma,Pandian Nagakannan,Rebecca E. Tweedell,Gustavo Palacios,Nathalie Becerra-Mora,Camenzind G. Robinson,Aaron Pitre,Peter Vogel,Taosheng Chen,Michael P. Murphy,Thirumala‐Devi Kanneganti
出处
期刊:Cell
[Cell Press]
日期:2025-11-28
卷期号:188 (25): 7155-7174.e25
被引量:49
标识
DOI:10.1016/j.cell.2025.11.002
摘要
The combination of innate immune activation and metabolic disruption plays critical roles in many diseases, often leading to mitochondrial dysfunction and oxidative stress that drive pathogenesis. However, mechanistic regulation under these conditions remains poorly defined. Here, we report a distinct lytic cell death mechanism induced by innate immune signaling and metabolic disruption, independent of caspase activity and previously described pyroptosis, PANoptosis, necroptosis, ferroptosis, and oxeiptosis. Instead, mitochondria undergoing BAX/BAK1/BID-dependent oxidative stress maintained prolonged plasma membrane contact, leading to local oxidative damage, a process we termed mitoxyperiosis. This process then caused membrane lysis and cell death, termed mitoxyperilysis. mTORC2 regulated the cell death, and mTOR inhibition restored cytoskeletal activity for lamellipodia to retract and mobilize mitochondria away from the membrane, preserving integrity. Activating this pathway in vivo regressed tumors in an mTORC2-dependent manner. Overall, our results identify a lytic cell death modality in response to the synergism of innate immune signaling and metabolic disruption.
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