Nitrate and Phosphate Transporters Rescue Fluoride Toxicity in Yeast

Stress-response pathways, especially oxidative stress responses, are activated in a broad cross-section of bacterial species upon fluoride challenge.

“Stress-response pathways, especially oxidative stress responses, are activated in a broad cross-section of bacterial species upon fluoride challenge21,88,95,97,101.”

Increased cytoplasmic phosphate is protective against fluoride toxicity.

“But there is also evidence that increased cytoplasmic phosphate is protective against fluoride toxicity88,97, perhaps partly due to phosphate’s buffering capacity at neutral pH.”

The depletion of NADPH and NADH could be explained by partial inhibition of redox-active dehydrogenases or by higher consumption of NAD(P)H to counter oxidative stress imposed by NaF.

“This observation could be explained either by the partial inhibition of redox‐active dehydrogenases, e.g. G6P dehydrogenase or the aforementioned isocitrate dehydrogenase, or because of higher rates of consumption of NAD(P)H to counterbalance the oxidative stress imposed by NaF (Johnston & Strobel, 2019).”

Fluoride ion (F−) is a common xenobiotic in natural environments that causes broad-spectrum harm to metabolic pathways.

“One particularly ancient, pernicious threat is posed by fluoride ion (F−), a common xenobiotic in natural environments that causes broad-spectrum harm to metabolic pathways.”

In yeast, fluoride resistance is imparted by the export of compounds like nitrates that contribute to oxidative stress, and the import of antioxidant metabolites like sulfite.

“In yeast, fluoride resistance is imparted by the export of compounds like nitrates that contribute to oxidative stress, and the import of antioxidant metabolites like sulfite97.”