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.

中文翻译：

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细胞毒性 T 细胞持续杀伤需要线粒体翻译

初始 CD8 ^{+的 T 细胞受体激活}T 淋巴细胞开始成熟为效应细胞毒性 T 淋巴细胞 (CTL)，它可以杀死癌症和病毒感染的细胞。尽管 CTL 在获得效应功能时显示出对糖酵解的依赖性增加，但我们发现线粒体在靶细胞杀伤中的基本要求。USP30（泛素羧基末端水解酶 30）中的急性线粒体耗竭——缺乏 CTL 显着降低了杀伤能力，尽管运动、信号传导和分泌都完好无损。出乎意料的是，线粒体需求与线粒体翻译有关，对线粒体翻译的抑制会损害 CTL 的杀伤力。受损的线粒体翻译触发了细胞溶质翻译的减弱，阻止了分泌的杀伤效应物的补充，并降低了 CTL 进行持续杀伤的能力。因此，