The memory of neuronal mitochondrial stress is inherited transgenerationally via elevated mitochondrial DNA levels
The memory of neuronal mitochondrial stress is inherited transgenerationally via elevated mitochondrial DNA levels
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神经元线粒体应激的记忆通过线粒体 DNA 水平升高进行跨代遗传
DOI：
10.1038/s41556-021-00724-8
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发表时间：
2021-08-02
影响因子：
21.3
通讯作者：
Tian, Ye
中科院分区：
文献类型：
--
作者：
Zhang, Qian;Wang, Zihao;Tian, Ye
父母所经历的压力记忆可以传递给后代，作为对未来挑战的预测。在这里，我们发现，神经元线粒体扰动诱导的系统性线粒体未折叠蛋白反应（UPRmt）在秀丽隐杆线虫可以传递给后代多代。UPRm的跨代激活是由线粒体DNA（mtDNA）水平升高的母系遗传介导的，这导致线粒体内的蛋白质稳态应激。此外，使用wildC.更进一步支持母系遗传较高水平mtDNA可诱导后代UPRm。丝裂因子Wnt信号通路是提高mtDNA水平跨代传递所必需的，从而赋予后代寿命延长和抗应激能力。总的来说，我们的研究结果表明，神经系统可以通过增加种系中的mtDNA来跨代传递压力信号，使后代能够更好地科普预期的挑战。
The memory of stresses experienced by parents can be passed on to descendants as a forecast of the challenges to come. Here, we discovered that the neuronal mitochondrial perturbation-induced systemic mitochondrial unfolded protein response (UPRmt) inCaenorhabditis eleganscan be transmitted to offspring over multiple generations. The transgenerational activation of UPRmtis mediated by maternal inheritance of elevated levels of mitochondrial DNA (mtDNA), which causes the proteostasis stress within mitochondria. Furthermore, results from intercrossing studies using wildC. elegansstrains further support that maternal inheritance of higher levels of mtDNA can induce the UPRmtin descendants. The mitokine Wnt signalling pathway is required for the transmission of elevated mtDNA levels across generations, thereby conferring lifespan extension and stress resistance to offspring. Collectively, our results reveal that the nervous system can transmit stress signals across generations by increasing mtDNA in the germline, enabling descendants to better cope with anticipated challenges.