The Molecular Basis of pH Sensing, Signaling, and Homeostasis in Fungi

Fungi mount efficient responses to altered extracellular pH. Characterization of the underlying mechanisms is fundamentally important in terms of understanding the molecular basis of pH homeostasis in higher eukaryotic cells, and for optimizing industrial processes which utilize fungi such as the production of pharmaceutical agents and food-use enzymes. Fungal pH adaptation is also a key requisite for establishment of multiple plant, insect, animal, and human diseases. Due to the differential reliance, respectively, of human and fungal cells upon electroneutral Na(+)-H(+) antiporters and outwardly directed electrogenic proton pumps, fundamental differences in the circuitry of pH homeostasis and adaptation exist, and these might be exploitable from a therapeutic perspective. At the molecular level, fungal pH tolerance is mediated by distinct but complementary homeostatic responses and highly conserved intracellular signaling pathways. Although traditionally studied as independent regulatory entities, the advent of systems biology has fuelled a new awareness of the interconnectivity between these very different modes of regulation. This review focuses upon the most recent advances in molecular understanding of three specific aspects of fungal pH adaptation, namely, sensing, signaling, and homeostasis.