Nathalie Tsimhoni
Pronouns: she/her
Research Mentor(s): Amy Chang
Research Mentor School/College/Department: MCDB / LSA
Program:
Authors: Nathalie Tsimhoni, Amy Chang
Session: Session 2 10:00- 10:50 a.m. Hussey Room
Poster:
Abstract
During Endoplasmic Reticulum Stress (ERS), which occurs in eukaryotes when the demand for properly folded proteins is greater than the ER can manage to fold, there is an increase in oxidative stress which causes damage to the cell (Knupp et al., 2018). The ER has two major mechanisms to help ameliorate the effects of ERS; the first is a transcriptional response called the Unfolded Protein Response (UPR), which upregulates chaperones to help fold up proteins, and the second response is to degrade misfolded proteins by ER Associated Protein Degradation (ERAD) (Oslowski et al. 2013). In previous research investigating cell death, the Chang Lab discovered that mitochondria contribute to the response to prolonged or extreme ER stress (Knupp et al. 2018). This is significant because ERS in humans contributes to diabetes and neurodegeneration; exploring the mechanisms behind ERS could lead to a deeper understanding of these conditions. Currently, the Chang Lab is investigating the mechanisms for how mitochondria adapt during ERS to ameliorate stress. Using a mito-dsRed construct (a fluorescent protein targeted to mitochondria), I have shown an increased import of proteins to the mitochondria during ERS. Most mitochondrial proteins are imported, so the upregulation of import by ERS illuminates the mechanisms by which mitochondria are remodeled during ERS. Additionally, I have shown that mitochondrial respiration and select proteins of the respiratory machinery are increased in response to ER stress using high-resolution respirometry and western blotting, respectively. My work further explores the role of pumilio-fem-3 (Puf3), a conserved mRNA binding protein that regulates mRNA localization and stability to downregulate specific proteins. Puf3 is degraded during ERS, allowing mitochondrial remodeling to occur by relieving negative regulation. My results highlight the role of mitochondria during ERS and suggest regulation by Puf3.
