Under stress conditions, mitochondria release low levels of reactive oxygen species (ROS), which triggers a cytoprotective response, called "mitohormesis". It still remains unclear how mitochondria respond to stress-derived stimuli and release a low level of ROS. Here, we show that N-acetyl-l-tyrosine (NAT) functions as a plausible intrinsic factor responsible for these tasks in stressed animals. NAT is present in the blood or hemolymph of healthy animals, and its concentrations increase in response to heat stress. Pretreatment with NAT significantly increases the stress tolerance of tested insects and mice. Analyses using Drosophila larvae and cultured cells demonstrate that the hormetic effects are triggered by transient NAT-induced perturbation of mitochondria, which causes a small increase in ROS production and leads to sequential retrograde responses: NAT-dependent FoxO activation increases in the gene expression of antioxidant enzymes and Keap1. Moreover, we find that NAT represses tumor growth, possibly via the activation of Keap1. In sum, we propose that NAT is a vital endogenous molecule that could serve as a triggering factor for mitohormesis.

中文翻译：

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N-乙酰基-L-酪氨酸是应激动物线粒体兴奋作用的内在触发因素。

在应激条件下，线粒体释放低水平的活性氧（ROS），从而引发细胞保护反应，称为“线粒体毒效作用”。目前仍不清楚线粒体如何响应应激刺激并释放低水平的活性氧。在这里，我们表明，N-乙酰基-L-酪氨酸（NAT）作为一种看似合理的内在因素，在应激动物中负责这些任务。NAT 存在于健康动物的血液或血淋巴中，其浓度会因热应激而增加。NAT 预处理显着提高了受试昆虫和小鼠的应激耐受性。使用果蝇幼虫和培养细胞进行的分析表明，毒物兴奋效应是由短暂的 NAT 诱导的线粒体扰动触发的，这会导致 ROS 产生小幅增加并导致连续的逆行反应：NAT 依赖性 FoxO 激活增加抗氧化剂基因表达酶和Keap1。此外，我们发现 NAT 可能通过激活 Keap1 来抑制肿瘤生长。总之，我们认为 NAT 是一种重要的内源性分子，可以作为线粒体毒效作用的触发因素。