Files
Download Full Text (1.2 MB)
Presentation date
Summer 7-10-2022
College, Institute, or Department
Pathology and Microbiology
Faculty Mentor
Leonardo da Silva Augusto
Research Mentor
Leonardo da Silva Augusto
Abstract
Toxoplasma gondii is an obligate intracellular parasite that reconfigures its host cell to promote pathogenesis. Toxoplasma is able to infect virtually all warm-blooded animals, and it is estimated that this parasite has infected nearly 2 billion people globally and approximately 25% of the US population. Curiously, upon infection Toxoplasma recruits the host cell’s endoplasmic reticulum (ER) and mitochondria into close proximity to the parasitophorous vacuole (PV), although the reasons for these high affinity interactions are not completely understood. It has been shown that Toxoplasma induces host mitochondria elongation to acquire fatty acids and establish a niche for itself. Our exciting new data showed that through the host ER-PV association, Toxoplasma actively induces the unfolded protein response (UPR), leading to PERK activation. Furthermore, new data suggests that PERK activation coordinates mitochondrial elongation. Therefore, we hypothesize that PERK activation induces mitochondrial elongation in Toxoplasma infected cells. Using immunofluorescence, we determined whether PERK activation plays a role in mitochondrial elongation induced by Toxoplasma infection. First, we confirmed that the Toxoplasma PV interacts with host mitochondria and ER. Next, we found that Toxoplasma infection promotes mitochondrial elongation and by using a pharmacological approach, we were able to inhibit PERK, which significantly decreased mitochondrial elongation. Our study has identified a novel mechanism used by Toxoplasma to induce mitochondrial elongation in order to acquire fatty acids, providing new insights into strategies for treatment of toxoplasmosis.
Keywords
toxoplasma, UPR, mitochondria, ER, PERK
Recommended Citation
Funke, Ethan J. and da Silva Augusto, Leonardo, "Intracellular Parasite Toxoplasma Exploits the Unfolded Protein Response to Acquire Mitochondrial Metabolites" (2022). Posters: 2022 Summer Undergraduate Research Program. 1.
https://digitalcommons.unmc.edu/surp2022/1