Abstract

Exposure of the yeast Saccharomyces cerevisiae to environmental stress can influence cell growth, physiology and differentiation, and thus result in a cell’s adaptive response. During the course of an adaptive response, the yeast vacuoles play an important role in protecting cells from stress. Vacuoles are dynamic organelles that are similar to lysosomes in mammalian cells. The defect of a lysosome’s function may cause various genetic and neurodegenerative diseases. The multi-subunit V-ATPase is the main regulator for vacuolar function and its activity plays a significant role in maintaining pH homeostasis. The V-ATPase is an ATP-driven proton pump which is required for vacuolar acidification. It has also been demonstrated that phospholipid biosynthetic genes might influence vacuolar morphology and function. However, the mechanistic link between phospholipid biosynthetic genes and vacuolar function has not been established. Recent studies have demonstrated that there is a regulatory role of Pah1p, a phospholipid biosynthetic gene, in V-ATPase disassembly and activity. Therefore, in this chapter we will use Saccharomyces cerevisiae as a model to discuss how Pah1p affects V-ATPase disassembly and activity and how Pah1p negatively affect vacuolar function. Furthermore, we propose a hypothesis to describe how Pah1p influences vacuolar function and programmed cell death through the regulation of V-ATPase.

Highlights

  • The yeast vacuole is a crucial and dynamic organelle necessary for the survival of the cell

  • This review aims to look at the significant role that V-ATPases play in maintaining pH homeostasis in yeast cells and how they are impacted by Pah1p, a key phosphatidate (PA) phosphatase in the lipid biosynthetic pathway that has been linked to apoptotic mechanisms via the regulation of this pump

  • The study of vacuolar function in Saccharomyces cerevisiae, and the activity of the V-ATPase pump is important since yeast vacuoles are strikingly similar to the lysosomes in mammalian cells [52

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Summary

Introduction

The yeast vacuole is a crucial and dynamic organelle necessary for the survival of the cell. Of particular importance are the vacuolar proton translocating ATPase (V-ATPase) pumps These energy requiring proton pumps are found in the membrane of the vacuole and can help defend the cell against many damaging environmental elements. Given the widespread localization of these pumps in various organelle membranes, V-ATPases are involved in a number of vital roles in cellular homeostasis including protein sorting and secretion, vesicular trafficking and zymogen activation [8]. They have been shown to be involved in endocytic and autophagic processes [1, 2, 9]. This review aims to look at the significant role that V-ATPases play in maintaining pH homeostasis in yeast cells and how they are impacted by Pah1p, a key phosphatidate (PA) phosphatase in the lipid biosynthetic pathway that has been linked to apoptotic mechanisms via the regulation of this pump

V-ATPase pump function
Structural composition of the vacuolar V-ATPase pump
V-ATPase subunit functions
V-ATPase mechanism of disassembly and assembly
Importance of V-ATPase activity in mammalian cells
Regulation of the lipid biosynthetic pathway
The role of PAH1 in vacuolar morphology and function
V-ATPases and glucose metabolism
10. V-ATPase and cancer
11. V-ATPase genes and the lipid biosynthetic pathway
12. A working model
13. Conclusion
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