Date of Award

Fall 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cell Biology

First Advisor

Colón-Ramos, Daniel

Abstract

While metabolic pathways are largely conserved across cells and organisms, tissues exhibit metabolic heterogeneity that tailors metabolism to their physiological demands. How the conserved pathways of metabolism achieve metabolic heterogeneity is incompletely understood, particularly in vivo. In this dissertation, I investigate the genetic requirement of glucose 6-phosphate isomerase (GPI-1), a conserved glycolytic enzyme that also regulates the pentose phosphate pathway (PPP). Using CRISPR-Cas9 genome editing, I found that gpi-1 knockout animals display germline defects consistent with impaired PPP, and somatic defects consistent with impaired glycolysis. I discovered that GPI-1 isoforms are differentially expressed and localized: GPI-1A is cytosolic in all tissues, whereas GPI-1B localizes to subcellular foci in the germline. Ectopic expression of GPI-1B in somatic tissues was sufficient to rescue glycolytic dysfunction in gpi-1 mutants, but did not fully reconstitute wild-type glycolytic dynamics. Moreover, disrupting GPI-1B's localization to the endoplasmic reticulum altered glycolytic dynamics, suggesting that subcellular targeting is critical for metabolic regulation. Together, these findings support a model in which isoform-specific localization of glycolytic proteins such as GPI-1 enables tissue-specific metabolic programs and physiological functions.

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