**1. Introduction**

The yeast vacuole is a crucial and dynamic organelle necessary for the survival of the cell. Adverse environmental factors, such as osmotic stress, toxic metal exposure, and alkaline pH conditions can wreak havoc on normal cellular processes and homeostasis. The vacuole helps play a critical role in protecting the cell via the induction of adaptive stress responses that are upregulated to shield the cell against many of these adverse environmental conditions. 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. These multi-subunit ATPase

complexes span the membrane and actively transport hydrogen ions into the lumen of the organelle. While V-ATPases have been highly characterized in vacuoles they are also present in a number of other organelles and cellular structures including lysosomes, Golgi complexes and the endosomes of eukaryotic cells [1–3]. Furthermore, in mammalian cells, these V-ATPase pumps have been found to be recruited to the cellular membranes of specialized cell types for the purpose of transporting protons across the membrane [1, 2].

Much of the research regarding V-ATPases has been conducted in the model system *Saccharomyces cerevisiae*. The main function of the V-ATPase pump is to acidify the organelle and maintain the internal acidic pH which is required for normal vacuolar function. Thus, the pump hydrolyzes ATP and drives the transport of protons across the membrane from the cytosol and into the lumen of the organelle [4]. The yeast vacuole is, in fact, one of the most highly acidic organelles documented in a cell, along with lysosomes in mammalian cells [4]. Vacuolar pH ranges in acidity from pH 5.0 to 6.5, depending on the specific environmental conditions [4–6]. In lysosomes, the internal pH is even lower, ranging from pH 4.5–5.0 [7]. 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]. Additionally, they have also been shown to be involved in endocytic and autophagic processes [1, 2, 9]. Since they play a vital position in maintaining cellular homeostasis, much research has been conducted to better understand just how important these pumps are. This review aims to specifically 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.
