Low phosphate mitigates cadmium-induced oxidative stress in Saccharomyces cerevisiae by enhancing endogenous...

Cadmium is a highly toxic heavy metal that causes many harmful effects on human health and ecosystems. Metal chelation-based techniques have become a common approach for the treatment of metal poisoning and also for the remediation of metal contamination. Phosphate, an essential nutrient required for key cellular functions, has been supposed to be effective in reducing cadmium bioavailability, possibly through its chelating potential. In this study, we explored the effects of phosphate on cadmium toxicity and cellular response to cadmium stress in the eukaryotic model Saccharomyces cerevisiae. Our results reveal that cadmium toxicity is unexpectedly enhanced during phosphate repletion and optimal phosphate levels for yeast growth under cadmium stress conditions decline with increasing cadmium concentrations. The profound cadmium toxicity during phosphate repletion is unlikely to result from either elevated cadmium accumulation or dysregulated homeostasis of essential metals, but rather due to increased production of intracellular reactive oxygen species. We show that, under phosphate-depleted conditions, the activities of antioxidant enzymes, especially Mn-superoxide dismutase and catalase, are significantly promoted through transcriptional upregulation. Our findings highlight the important role of cellular response to phosphate limitation in mitigating cadmium toxicity and endogenous oxidative stress through the enhancement of antioxidant enzyme activity.