细胞毒性T细胞(CTL)持续杀伤需要线粒体翻译，这一成果由英国剑桥大学Gillian M. Griffiths团队经过不懈努力而取得。相关论文于2021年10月15日发表在《科学》杂志上。

尽管CTL在获得效应子功能时表现出对糖酵解的依赖性增加，但研究人员发现线粒体在杀死靶细胞时必不可少。线粒体中USP30（泛素羧基末端水解酶30）的急性耗竭导致CTL杀伤能力显著降低，尽管运动性、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，抑制线粒体翻译会损害CTL杀伤。受损的线粒体翻译导致细胞质翻译减弱，阻碍分泌性杀伤效应物的补充，并降低CTL进行持续杀伤的能力。因此，线粒体作为一种以前未被重视的蛋白质翻译稳态调节器出现，这是CTL发挥连续杀伤功能所需的。

据介绍，新生CD8⁺ T淋巴细胞的T细胞受体激活促进其分化为效应细胞毒性T淋巴细胞(CTL)，它可以杀死癌症和病毒感染的细胞。

附：英文原文

Title: Mitochondrial translation is required for sustained killing by cytotoxic T cells

Author: Miriam Lisci, Philippa R. Barton, Lyra O. Randzavola, Claire Y. Ma, Julia M. Marchingo, Doreen A. Cantrell, Vincent Paupe, Julien Prudent, Jane C. Stinchcombe, Gillian M. Griffiths

Issue&Volume: 2021-10-15

Abstract: T cell receptor activation of nave 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.

DOI: abe9977

Source: https://www.science.org/doi/10.1126/science.abe9977