University of Texas Health Science Center at Houston
Unveiling the Intercompartmental Signaling Axis: Mitochondrial to ER Stress Response (MERSR) and Its Impact on Proteostasis
Abstract
dc:description.abstract<p>Maintaining protein homeostasis is essential for cellular health. During times of protein stress, cells deploy unique defense mechanisms to achieve resolution. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response (MCSR), a unique stress response activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2a signaling pathway, increasing phosphorylation of eIF2a and improving the ER’s capacity to manage greater proteostasis load. MERSR activation in both poly-glutamine (poly-Q) and amyloid-beta (Aß) C. elegans disease models also leads to improvement in both aggregate burden and overall disease outcome. These findings shed light on the coordination between the mitochondria and the ER in maintaining cellular proteostasis and provide further evidence for the importance of intercompartmental signaling.</p>
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy (PhD)
- Level thesis:degree_level
- Dissertation (PhD)
- Year dc:date.available
- 2024
Author and committee
dc:creator, dc:contributor.*- Authors dc:creator
-
- Li, Jeson
- <p>0000-0001-6387-5910</p>
- Contributors dc:contributor
-
- Hyun-Eui Kim, Ph.D.
- Jian Hu, Ph.D.
- Jeff Frost, Ph.D.
Subjects
dc:subject × 8Identifiers
dc:identifier.*- Repository record dc:identifier
- https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1381
- OAI identifier oai:identifier
- oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2438