**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 multisubunit 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.

**Keywords:** Phospholipid biosynthesis, Pah1p, programmed cell death, vacuolar activity, V-ATPase, pH homeostasis, Hxk2p
