期刊
NATURE CELL BIOLOGY
卷 23, 期 8, 页码 870-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41556-021-00724-8
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资金
- NIH-Officer of Research Infrastructure Programs [P40 OD010440]
- Japanese National BioResource Project
- National Key R&D Program of China [2017YFA0506400, 2019YFA0508700]
- Strategic Priority Research Program of Chinese Academy of Sciences [XDB39000000]
- National Natural Science Foundation of China [31930023, 31771333, 31922014]
Parental stress memories can be passed on to offspring by elevating mitochondrial DNA levels, inducing UPRmt in the next generation to better cope with challenges.
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) in Caenorhabditis elegans can be transmitted to offspring over multiple generations. The transgenerational activation of UPRmt 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 UPRmt 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. Zhang et al. report that the systemic mitochondrial unfolded protein response triggered by neuronal mitochondrial stress can be transmitted across multiple generations in Caenorhabditiselegans via a mechanism involving elevation in mitochondrial DNA levels in oocytes.
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