细胞毒性T细胞
CTL公司*
效应器
翻译(生物学)
胞浆
细胞生物学
生物
CD8型
线粒体
生物化学
信使核糖核酸
免疫学
免疫系统
体外
酶
基因
作者
Miriam Lisci,P. J. Barton,Lyra O Randzavola,Y. Claire,Julia M. Marchingo,Doreen A. Cantrell,V. Semet,Julien Prudent,Jane C. Stinchcombe,Gillian M. Griffiths
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2021-10-15
卷期号:374 (6565)
被引量:53
标识
DOI:10.1126/science.abe9977
摘要
T cell receptor activation of naïve CD8+ T lymphocytes initiates their maturation into effector cytotoxic T lymphocytes (CTLs), which can kill cancer and virally infected cells. Although CTLs show an increased reliance on glycolysis upon acquisition of effector function, we found an essential requirement for mitochondria in target cell–killing. Acute mitochondrial depletion in USP30 (ubiquitin carboxyl-terminal hydrolase 30)–deficient CTLs markedly diminished killing capacity, although motility, signaling, and secretion were all intact. Unexpectedly, the mitochondrial requirement was linked to mitochondrial translation, inhibition of which impaired CTL killing. Impaired mitochondrial translation triggered attenuated cytosolic translation, precluded replenishment of secreted killing effectors, and reduced the capacity of CTLs to carry out sustained killing. Thus, mitochondria emerge as a previously unappreciated homeostatic regulator of protein translation required for serial CTL killing.
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