The role of ion homeostasis in adaptation and tolerance to acetic acid stress in yeasts

Abstract

Maintenance of asymmetric ion concentrations across cellular membranes is crucial for proper yeast cellular function. Disruptions of these ionic gradients can significantly impact membrane electrochemical potential and the balance of other ions, particularly under stressful conditions such as exposure to acetic acid. This weak acid, ubiquitous to both yeast metabolism and industrial processes, is a major inhibitor of yeast cell growth in industrial settings and a key determinant of host colonization by pathogenic yeast. Acetic acid toxicity depends on medium composition, especially on the pH (H+ concentration), but also on other ions' concentrations. Regulation of ion fluxes is essential for effective yeast response and adaptation to acetic acid stress. However, the intricate interplay among ion balancing systems and stress response mechanisms still presents significant knowledge gaps. This review offers a comprehensive overview of the mechanisms governing ion homeostasis, including H+, K+, Zn2+, Fe2+/3+, and acetate, in the context of acetic acid toxicity, adaptation, and tolerance. While focus is given on Saccharomyces cerevisiae due to its extensive physiological characterization, insights are also provided for biotechnologically and clinically relevant yeast species whenever available.

Keywords: H+ homeostasis; K+ homeostasis; ion fluxes; response to stress; stress tolerance; weak acids.

Figure 1.

Illustration of the mechanisms of toxicity induced by acetic acid in S. cerevisiae. Brief descriptions of each of the enumerated acetic acid toxicity processes are provided in Table 1.

Figure 2.

Illustration of the mechanisms of response and adaptation, reported and proposed for S. cerevisiae, to acetic acid stress through the regulation of ion homeostasis and fluxes. Some of these mechanisms are included in Table 1. Kinases and phosphatases are displayed in yellow and pink, respectively. Transcription factors are displayed in purple. Membrane proteins reported to be associated with acetic acid stress tolerance are represented in red. Pma1 is shown in the monomeric form to convey the mechanisms of regulation. Dashed arrows refer to putative or indirect associations.