A Genome-Wide Screen in Saccharomyces cerevisiae Reveals a Critical Role for Oxidative Phosphorylation in Cellular Tolerance to Lithium Hexafluorophosphate.

Lithium hexafluorophosphate (LiPF ₆ ) is one of the leading electrolytes in lithium-ion batteries, and its usage has increased tremendously in the past few years. Little is known, however, about its potential environmental and biological impacts. In order to improve our understanding of the cytotoxicity of LiPF ₆ and the specific cellular response mechanisms to it, we performed a genome-wide screen using a yeast ( Saccharomyces cerevisiae ) deletion mutant collection and identified 75 gene deletion mutants that showed LiPF ₆ sensitivity. Among these, genes associated with mitochondria showed the most enrichment. We also found that LiPF ₆ is more toxic to yeast than lithium chloride (LiCl) or sodium hexafluorophosphate (NaPF ₆ ). Physiological analysis showed that a high concentration of LiPF ₆ caused mitochondrial damage, reactive oxygen species (ROS) accumulation, and ATP content changes. Compared with the results of previous genome-wide screening for LiCl-sensitive mutants, we found that oxidative phosphorylation-related mutants were specifically hypersensitive to LiPF ₆ . In these deletion mutants, LiPF ₆ treatment resulted in higher ROS production and reduced ATP levels, suggesting that oxidative phosphorylation-related genes were important for counteracting LiPF ₆ -induced toxicity. Taken together, our results identified genes specifically involved in LiPF ₆ -modulated toxicity, and demonstrated that oxidative stress and ATP imbalance maybe the driving factors in governing LiPF ₆ -induced toxicity.