The Where, When, and How of Organelle Acidification by the Yeast Vacuolar H ⁺ -ATPase

Abstract

SUMMARY All eukaryotic cells contain multiple acidic organelles, and V-ATPases are central players in organelle acidification. Not only is the structure of V-ATPases highly conserved among eukaryotes, but there are also many regulatory mechanisms that are similar between fungi and higher eukaryotes. These mechanisms allow cells both to regulate the pHs of different compartments and to respond to changing extracellular conditions. The Saccharomyces cerevisiae V-ATPase has emerged as an important model for V-ATPase structure and function in all eukaryotic cells. This review discusses current knowledge of the structure, function, and regulation of the V-ATPase in S. cerevisiae and also examines the relationship between biosynthesis and transport of V-ATPase and compartment-specific regulation of acidification.

Deletion of Vacuolar Proton-translocating ATPase Voa Isoforms Clarifies the Role of Vacuolar pH as a Determinant of Virulence-associated Traits in Candida albicans*

“…2) was surprising, given that S. cerevisiae vph1⌬ mutants display a mild vma phenotype (41). C. albicans vma7⌬/⌬ (V 1 F) mutants, which presumably lack all cellular V-ATPase function, display significant pH-dependent growth defects in C. albicans (9), thereby resembling S. cerevisiae vma⌬ mutants (2,13). We anticipate that loss of both V o a isoforms, which also eliminates V-ATPase function completely, will be necessary to develop pH-dependent growth impairment (vma phenotype) in C. albicans as in S. cerevisiae.…”

“…albicans infectivity involves mechanisms interrelated with vacuolar and/or V-ATPase functions (2,13) that depend on the expression of virulence factors, a set of genes and proteins that influence the numerous pathways used by C. albicans (14). For example, C. albicans secretes aspartyl proteinases and lipases that are involved in nutrient acquisition, host cell degradation, and immune evasion (15).…”

Pathway swapping: Toward modular engineering of essential cellular processes

“…Another factor potentially involved in the slow growth phenotype of SwYG is the secondary function, unrelated to their catalytic role in glycolysis, of three glycolytic enzymes (36), which may be affected by the genetic relocalization. However, involvement of these secondary functions in the slow growth phenotype of SwYG does not appear very likely as the vacuolar role of Fba1 and Eno2 is not expected to lead to visible growth defects under acidic environments (the pH used was ≤6) (37,38) and the physiological characterization of SwYG did not suggest an altered regulatory activity of Hxk2 (39). Alternatively, we cannot rule out that factors external to the clustering and relocalization of glycolytic genes are responsible for the slower growth of SwYG.…”

A research‐based laboratory course designed to strengthen the research‐teaching nexus

“…Mechanical rotation of a central shaft that extends from V 1 to V o and consists of various subunits, including the subunit d, couples ATP hydrolysis, and proton transport. The structural complexity of these membrane transporters, their fascinating mechanism of rotational catalysis, and their link to several types of cancers and kidney, muscle, and bone diseases [8][9][10][11] helped capture the research laboratory course students' attention and curiosity. The yeast S. cerevisiae was employed as the model organism in this research laboratory course not only because it is the system used by the primary author in her own work, but because it is an inexpensive, safe, and powerful research tool suitable for undergraduate research and teaching [12][13][14][15][16].…”

“…Mechanical rotation of a central shaft that extends from V 1 to V o and consists of various subunits, including the subunit d, couples ATP hydrolysis, and proton transport. The structural complexity of these membrane transporters, their fascinating mechanism of rotational catalysis, and their link to several types of cancers and kidney, muscle, and bone diseases [8][9][10][11] helped capture the research laboratory course students' attention and curiosity.…”