RRC ID 75919
著者 Campos JC, Wu Z, Rudich PD, Soo SK, Mistry M, Ferreira JC, Blackwell TK, Van Raamsdonk JM.
タイトル Mild mitochondrial impairment enhances innate immunity and longevity through ATFS-1 and p38 signaling.
ジャーナル EMBO Rep
Abstract 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.
巻・号 22(12)
ページ e52964
公開日 2021-12-6
DOI 10.15252/embr.202152964
PMID 34617666
PMC PMC8647147
MeSH Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Immunity, Innate / physiology Longevity* / genetics Mitochondria / genetics Mitochondria / metabolism Signal Transduction
リソース情報
線虫 tm6724