Yiting Xu / Biology / Faculty Mentor: Mark Pellegrino
Bacterial pathogens use a variety of mechanisms to foster their infection in the host, including the manipulation of host organelles that will support their survival. Mitochondria are a prime target for pathogens since they mediate critical cell functions including the generation of energy and the regulation of cell death programs such as apoptosis. Cells mount various responses to repair the damage incurred by mitochondria during infection and other stresses. One such pathway is the mitochondrial unfolded protein response (UPRmt), a stress response that transcriptionally regulates mitoprotective gene expression. In the model organism Caenorhabditis elegans, the UPRmt also regulates an innate immunity pathway that helps promote host survival during infection. We previously discovered that the UPRmt is activated when C. elegans is infected with the bacterial pathogen Pseudomonas aeruginosa. However, the UPRmt is repressed during chronic infection, but can be reversed upon supplementation with the amino acid valine. Here, we show that the valine supplementation activates the homeodomain transcription factor MLS-2. We find that MLS-2 acts cell non-autonomously in the nervous system to regulate the UPRmt in the intestine, promoting the survival of the C. elegans host. Curiously, our genetic approaches suggest that MLS-2 stimulates the UPRmt by modulating energy metabolism.
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