Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection Journal Article
| Authors: | Pellegrino, M. W.; Nargund, A. M.; Kirienko, N. V.; Gillis, R.; Fiorese, C. J.; Haynes, C. M. |
| Article Title: | Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection |
| Abstract: | Metazoans identify and eliminate bacterial pathogens in microbe-rich environments such as the intestinal lumen; however, themechanisms are unclear.Host cells could potentially use intracellular surveillance or stress response programs to detect pathogens that targetmonitored cellular activities andthen initiate innate immune responses1-3.Mitochondrial function is evaluated bymonitoringmitochondrial protein import efficiency of the transcription factorATFS-1,whichmediates the mitochondrial unfolded protein response (UPRmt). Duringmitochondrial stress, mitochondrial import is impaired4, allowing ATFS-1 to traffic to the nucleus where it mediates a transcriptional response to re-establish mitochondrial homeostasis5. Here we examined the role of ATFS-1 inCaenorhabditis elegans during pathogen exposure, because during mitochondrial stressATFS-1 induced not onlymitochondrial protective genes but also innate immunegenes that included a secreted lysozyme and anti-microbial peptides. Exposure to the pathogen Pseudomonas aeruginosa caused mitochondrial dysfunction and activation of the UPRmt. C. elegans lacking atfs-1 were susceptible to P. aeruginosa, whereas hyper-activation of ATFS-1 and the UPRmt improved clearance of P. aeruginosa from the intestine and prolonged C. elegans survival in a manner mainly independent of knowninnate immune pathways6,7.Wepropose thatATFS-1 import efficiency and the UPRmt is a means to detect pathogens that target mitochondria and initiate a protective innate immune response. |
| Keywords: | bacteria (microorganisms); caenorhabditis elegans; metazoa; pseudomonas aeruginosa |
| Journal Title: | Nature |
| Volume: | 516 |
| Issue: | 7531 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2014-12-18 |
| Start Page: | 414 |
| End Page: | 417 |
| Language: | English |
| DOI: | 10.1038/nature13818 |
| PROVIDER: | scopus |
| PMCID: | PMC4270954 |
| PUBMED: | 25274306 |
| DOI/URL: | |
| Notes: | Export Date: 2 March 2015 -- Source: Scopus |
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