PI(3,5)P2 enhances V-ATPase activity and Vcx1 hyperactivity inhibits proton acquisition in yeast vacuoles

Rivera-Kohr, David A.

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https://hdl.handle.net/2142/117048 Copy

Description

Title

PI(3,5)P2 enhances V-ATPase activity and Vcx1 hyperactivity inhibits proton acquisition in yeast vacuoles

Author(s)

Rivera-Kohr, David A.

Issue Date

2020-05

Keyword(s)

• yeast
• vacuole
• V-ATPase
• Vcx1
• PI(3,5)P2

Language

en

Abstract

The acidification of vacuoles and lysosomes is critical for eukaryotic cells to function properly. However, the factors which modulate the acidity of these organelles are not fully understood. I used genetic techniques to generate mutant yeast strains with modified vacuoles. Using fluorescence assays and microscopy to monitor proton transport in wild type and mutant vacuoles, I investigated the effects of phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), calcium ions and various protein inhibitors on vacuole acidification. Here I show PI(3,5)P2 enhances proton import through the V-ATPase and high doses of calcium inhibit proton influx by activating Ca2+/H+ exchanger Vcx1 [in vivo corroboration or contradiction has yet to be determined]. These findings elucidate the dynamics of proton flux at the vacuole and more broadly demonstrate how organelles can regulate acidity. Given the role of defective PI(3,5)P2 homeostasis and improper lysosome acidification in several diseases this study provides potential avenues toward improving our understanding and treatment of these diseases.

Graduation Semester

2023-01-09T21:45:44-06:00

Type of Resource

text

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