Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection
Pellegrino, Mark W.
Nargund, Amrita M.
Fiorese, Christopher J.
Haynes, Cole M.
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CitationPellegrino, Mark W., Amrita M. Nargund, Natalia V. Kirienko, Reba Gillis, Christopher J. Fiorese, and Cole M. Haynes. 2014. “Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection.” Nature 516 (7531): 414-417. doi:10.1038/nature13818. http://dx.doi.org/10.1038/nature13818.
AbstractMetazoans identify and eliminate bacterial pathogens in microbe-rich environments such as the intestinal lumen, however the mechanisms are unclear. Potentially, host cells employ intracellular surveillance or stress response programs to detect pathogens that target monitored cellular activities to initiate innate immune responses1–3. Mitochondrial function is evaluated by monitoring mitochondrial protein import efficiency of the transcription factor ATFS-1, which mediates the mitochondrial unfolded protein response (UPRmt). During mitochondrial stress, 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 during pathogen exposure because in addition to mitochondrial protective genes, ATFS-1 induced innate immune genes during mitochondrial stress that included a secreted lysozyme and anti-microbial peptides. Exposure to the pathogen Pseudomonas aeruginosa caused mitochondrial dysfunction and activation of the UPRmt. Animals lacking atfs-1 were susceptible to P. aeruginosa, while hyper-activation of ATFS-1 and the UPRmt improved clearance of P. aeruginosa from the intestine and prolonged C. elegans survival largely independent of known innate immune pathways6,7. We propose that ATFS-1 import efficiency and the UPRmt is a means to detect pathogens that target mitochondria and initiate a protective innate immune response.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:17295693
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