Graduation Semester and Year
Spring 2025
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Quantitative Biology
Department
Biology
First Advisor
Mark Pellegrino
Second Advisor
Piya Ghose
Third Advisor
Clay Clark
Fourth Advisor
Subhrangsu S. Mandal
Fifth Advisor
Cara Boutte
Abstract
The lifespan of an organism is dictated by various genetic and environmental factors. One such determinant is the health of mitochondria which are organelles that mediate various critical cell functions including a significant role in generating the vast supply of cellular energy. Indeed, the gradual decline of mitochondrial function is believed to be a hallmark and possible cause of aging. Paradoxically, mild mitochondrial dysfunction early in life extends lifespan in various model organisms. Cells use diverse approaches to promote mitochondrial homeostasis, including the transcriptional reprogramming of cells by mitochondrial unfolded protein response (UPRmt) to mitigate mitochondrial stress. Consistently, UPRmt activation is correlated with mitochondrial stress conditions that prolong animal longevity including mild defects in mitochondrial respiration and mitochondrial translation. We have previously shown that changes in nutrient availability can activate the UPRmt and extend lifespan, specially through the restriction of the amino acid methionine. However, a detailed mechanistic insight into this relationship is lacking. Here, we leveraged the powerful genetics of the model organism Caenorhabditis elegans to dissect the regulation of the UPRmt and lifespan resulting from methionine restriction. Using this approach, we have identified novel regulators of methionine restriction associated UPRmt activity and lifespan extension including neuropeptide signaling and the canonical TGF-beta signaling pathway.
Keywords
Metabolism, stress, mitochondria
Disciplines
Bioinformatics | Cell Biology | Developmental Biology | Genetics | Genomics | Immunity | Organismal Biological Physiology | Other Animal Sciences | Pathogenic Microbiology
License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
dodge, josh D., "Genetic analysis of methionine restriction-associated mitochondrial unfolded protein response signaling." (2025). Biology Dissertations. 228.
https://mavmatrix.uta.edu/biology_dissertations/228
Included in
Bioinformatics Commons, Cell Biology Commons, Developmental Biology Commons, Genetics Commons, Genomics Commons, Immunity Commons, Organismal Biological Physiology Commons, Other Animal Sciences Commons, Pathogenic Microbiology Commons