Genome-Wide Identification of Genes Involved in General Acid Stress and Fluoride Toxicity in Saccharomyces cerevisiae

Frontiers in Microbiology
Nichole R JohnstonScott A Strobel

Abstract

Hydrofluoric acid elicits cell cycle arrest through a mechanism that has long been presumed to be linked with the high affinity of fluoride to metals. However, we have recently found that the acid stress from fluoride exposure is sufficient to elicit many of the hallmark phenotypes of fluoride toxicity. Here we report the systematic screening of genes involved in fluoride resistance and general acid resistance using a genome deletion library in Saccharomyces cerevisiae. We compare these to a variety of acids - 2,4-dinitrophenol, FCCP, hydrochloric acid, and sulfuric acid - none of which has a high metal affinity. Pathways involved in endocytosis, vesicle trafficking, pH maintenance, and vacuolar function are of particular importance to fluoride tolerance. The majority of genes conferring resistance to fluoride stress also enhanced resistance to general acid toxicity. Genes whose expression regulate Golgi-mediated vesicle transport were specific to fluoride resistance, and may be linked with fluoride-metal interactions. These results support the notion that acidity is an important and underappreciated principle underlying the mechanisms of fluoride toxicity.

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Citations

Oct 8, 2021·Critical Reviews in Biotechnology·Diogo A M AlexandrinoMaria F Carvalho

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Methods Mentioned

BETA
Assay
Genetic Knockout
NMR
GTPases

Key Resources (RRID) Mentioned

SCR_005223
SCR_015828
SCR_005748
SCR_006786
SCR_002798

Software Mentioned

WebGestalt
prism
GraphPad Prism
ClueGO
Cytoscape
MCode

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