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.

Available for download on Wednesday, May 31, 2028

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