Graduation Year
2025
Document Type
Master's Thesis
Degree
Master of Science
Program
Biological Science
Partner Organization
Buck Institute for Research on Aging
Program Director
Patti Culross, MD, MPH
First Reader
Chuankai Zhou, PhD
Second Reader
Seungmin Yoo
Abstract
Lysosomal pH regulation is essential for proper cellular function, influencing degradation, recycling, and signaling pathways that maintain homeostasis. In this study, we investigated a rapid lysosomal acidification process induced by nutrient starvation. Using the pH Lysosomal Activity Reporter (pHLARE) biosensor, we observed an immediate decrease in sfGFP fluorescence, indicating a sharp increase in lysosomal acidity within 5 seconds induced by nutrient starvation. To determine whether nutrient deprivation was responsible for this acidification, we added amino acids, vitamins, glucose, and salts back to the medium. While amino acid supplementation partially restored sfGFP fluorescence within 30 minutes to 1 hour, it failed to suppress the rapid lysosome acidification, suggesting that additional factor(s) are responsible for the induced rapid lysosomal acidification. Understanding this rapid lysosomal acidification may provide new insights into cellular adaptation mechanisms and potential therapeutic targets for lysosome-associated diseases.