Molecular Targets Program, James Graham Brown Cancer Center, Departments of Medicine, Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA.
Institute of Technical Biology and Agriculture Engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
Cell Microbiol. 2018 Jan;20(1). doi: 10.1111/cmi.12787. Epub 2017 Oct 9.
N-(3-Oxododecanoyl)-l-homoserine lactone (C12) is produced by Pseudomonas aeruginosa to function as a quorum-sensing molecule for bacteria-bacteria communication. C12 is also known to influence many aspects of human host cell physiology, including induction of cell death. However, the signalling pathway(s) leading to C12-triggered cell death is (are) still not completely known. To clarify cell death signalling induced by C12, we examined mouse embryonic fibroblasts deficient in "initiator" caspases or "effector" caspases. Our data indicate that C12 selectively induces the mitochondria-dependent intrinsic apoptotic pathway by quickly triggering mitochondrial outer membrane permeabilisation. Importantly, the activities of C12 to permeabilise mitochondria are independent of activation of both "initiator" and "effector" caspases. Furthermore, C12 directly induces mitochondrial outer membrane permeabilisation in vitro. Overall, our study suggests a mitochondrial apoptotic signalling pathway triggered by C12, in which C12 or its metabolite(s) acts on mitochondria to permeabilise mitochondria, leading to activation of apoptosis.
N-(3-氧代十二烷酰基)-L-高丝氨酸内酯（C12）由铜绿假单胞菌产生，作为细菌-细菌通信的群体感应分子发挥作用。C12 也被认为会影响人体宿主细胞生理的许多方面，包括诱导细胞死亡。然而，导致 C12 触发细胞死亡的信号通路（s）仍不完全清楚。为了阐明 C12 诱导的细胞死亡信号，我们研究了缺乏“起始”半胱氨酸蛋白酶或“效应”半胱氨酸蛋白酶的小鼠胚胎成纤维细胞。我们的数据表明，C12 通过快速触发线粒体外膜通透性选择性地诱导线粒体依赖性内在凋亡途径。重要的是，C12 使线粒体通透性的作用独立于“起始”和“效应”半胱氨酸蛋白酶的激活。此外，C12 在体外直接诱导线粒体外膜通透性。总的来说，我们的研究表明 C12 触发了一种线粒体凋亡信号通路，其中 C12 或其代谢物（s）作用于线粒体以通透线粒体，导致凋亡的激活。
