RRC ID 76105
Author Zhang Q, Wang Z, Zhang W, Wen Q, Li X, Zhou J, Wu X, Guo Y, Liu Y, Wei C, Qian W, Tian Y.
Title The memory of neuronal mitochondrial stress is inherited transgenerationally via elevated mitochondrial DNA levels.
Journal Nat Cell Biol
Abstract 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.
Volume 23(8)
Pages 870-880
Published 2021-8-1
DOI 10.1038/s41556-021-00724-8
PII 10.1038/s41556-021-00724-8
PMID 34341532
MeSH Caenorhabditis elegans Proteins / genetics* DNA, Mitochondrial / metabolism* Genes, Mitochondrial* HEK293 Cells Humans Longevity / genetics Maternal Inheritance* Neurons / metabolism* Organelle Biogenesis Stress, Physiological / genetics* Unfolded Protein Response / genetics* Wnt Signaling Pathway
Resource
C.elegans