期刊
EMBO REPORTS
卷 22, 期 12, 页码 -出版社
WILEY
DOI: 10.15252/embr.202152964
关键词
aging; C; elegans; innate immunity; mitochondria; mitochondrial unfolded protein response
资金
- Canadian Institutes of Health Research (CIHR) [399148, 416150]
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-201904302]
- National Institute of General Medical Sciences (NIGMS) [R01 GM121756]
- Fonds de Recherche du Quebec Sante (FRQS)
- Parkinson Quebec
- FRQS
- NIH [R35 GM122610, R01 AG054215, P30 DK036836]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP 2019/18444-9]
- Shanghai Pujiang Program
- NIH Office of Research Infrastructure Programs [P30 OD010440]
Disrupting subunits of the mitochondrial electron transport chain results in the upregulation of genes involved in innate immunity, which promotes increased resistance to bacterial pathogens and extended longevity in long-lived mitochondrial mutants. Both the p38-mediated innate immune signaling pathway and the mitoUPR act together on the same innate immunity genes to modulate lifespan.
While mitochondrial function is essential for life in all multicellular organisms, a mild impairment of mitochondrial function can extend longevity in model organisms. By understanding the molecular mechanisms involved, these pathways might be targeted to promote healthy aging. In studying two long-lived mitochondrial mutants in C. elegans, we found that disrupting subunits of the mitochondrial electron transport chain results in upregulation of genes involved in innate immunity, which is driven by the mitochondrial unfolded protein response (mitoUPR) but also dependent on the canonical p38-mediated innate immune signaling pathway. Both of these pathways are required for the increased resistance to bacterial pathogens and extended longevity of the long-lived mitochondrial mutants, as is the FOXO transcription factor DAF-16. This work demonstrates that both the p38-mediated innate immune signaling pathway and the mitoUPR act in concert on the same innate immunity genes to promote pathogen resistance and longevity and that input from the mitochondria can extend longevity by signaling through these pathways. This indicates that multiple evolutionarily conserved genetic pathways controlling innate immunity also function to modulate lifespan.
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