Degree
Doctor of Philosophy (PhD)
Department
Biological Sciences
Document Type
Dissertation
Abstract
Organelle dynamics lie at the heart of cellular signaling and metabolic regulation, orchestrating physiological processes such as reproduction and aging across the lifespan. In this dissertation, I investigate how organelle-based signaling coordinates sperm activation and modulates organismal aging in the nematode Caenorhabditis elegans. I identify SPIN-4, a previously uncharacterized Spinster family transporter, as a key regulator of spermiogenesis. SPIN-4 is strongly expressed in developing sperm, localizes to the plasma membrane, and promotes sperm activation by facilitating the export of sphingosine-1-phosphate (S1P). Loss of spin-4 results in defective pseudopod formation, reduced motility, and compromised fertility, phenotypes that can be rescued by exogenous S1P. These findings uncover a novel lipid-based signaling mechanism required for functional sperm activation and suggest conservation of S1P-mediated motility across systems.
In the second part of this work, I examine how peroxisome dynamics influence mitochondrial integrity and lifespan. I show that age-associated degradation of peroxisomes via autophagy destabilizes mitochondrial networks, increases calcium burden, elevates oxidative stress, and reduces organism mobility. Inhibition of peroxisome fission through knockdown of prx-11 prevents pexophagy, preserving both peroxisome and mitochondrial homeostasis. This results in improved muscle function and lifespan extension without eliciting canonical stress responses. Importantly, long-lived mitochondrial mutants also exhibit delayed peroxisome degradation, and forced pexophagy in these backgrounds shortens lifespan, highlighting peroxisomal preservation as a shared feature of longevity.
To support future mechanistic studies, I have generated transcriptomic profiles of control and prx-11RNAi animals at key aging stages. Although not analyzed in this thesis, these datasets will enable the identification of regulators of mitochondrial maintenance, biogenesis, and potential signaling mediators of peroxisome–mitochondria communication. Together, this work positions organelle communication as a central logic of physiological resilience. By showing that targeted modulation of peroxisomal turnover or lipid signaling can reprogram aging and fertility trajectories, it opens conceptual and therapeutic avenues for enhancing cellular vitality across the lifespan.
Date
6-30-2025
Recommended Citation
Flora, Yash, "Metabolic and Physiological Regulation in C. elegans: Insights into Sperm Activation and Peroxisome-Mediated Longevity" (2025). LSU Doctoral Dissertations. 6828.
https://repository.lsu.edu/gradschool_dissertations/6828
Committee Chair
Bohnert, Adam K.
DOI
10.31390/gradschool_dissertations.6828