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 (UPR^mt) in Caenorhabditis elegans can be transmitted to offspring over multiple generations. The transgenerational activation of UPR^mt is mediated by maternal inheritance of elevated levels of mitochondrial DNA (mtDNA), which causes the proteostasis stress within mitochondria. Furthermore, results from intercrossing studies using wild C. elegans strains further support that maternal inheritance of higher levels of mtDNA can induce the UPR^mt in 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.

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，我们发现秀丽隐杆线虫中神经元线粒体扰动诱导的全身性线粒体未折叠蛋白反应 (UPR ^mt )可以通过多代传递给后代。^{UPR mt}的跨代激活是由线粒体 DNA (mtDNA) 水平升高的母系遗传介导的，这会导致线粒体内的蛋白质稳态压力。此外，使用野生C. elegans菌株的交叉研究结果进一步支持更高水平的 mtDNA 的母系遗传可以诱导 UPR ^mt在后代。mitokine Wnt 信号通路是跨代传递升高的 mtDNA 水平所必需的，从而赋予后代延长寿命和抗逆性。总的来说，我们的研究结果表明，神经系统可以通过增加生殖系中的 mtDNA 来跨代传递压力信号，使后代能够更好地应对预期的挑战。