Abstract
Bisphenol A, an endocrine-disrupting compound, is widely used in the industrial production of plastic products. Despite increasing concerns about its harmful effects on human health, animals, and the environment, the use of BPA has been banned only in infant products, and its effects on cellular processes are not fully understood. To investigate the impact of BPA on eukaryotic cells, we analyzed the proteome changes of wild-type and PDR5-deleted S. cerevisiae strains exposed to different doses of BPA using sample multiplexing-based proteomics. We found that the ABC multidrug transporter Pdr5 plays an important role in protecting yeast cells from BPA toxicity, with its absence significantly sensitizing cells to BPA. BPA inhibited yeast growth in a dose-dependent manner, with a more pronounced effect in PDR5-deleted cells. Proteomic analysis revealed that BPA induces widespread dose-dependent changes in protein abundance, including the upregulation of metabolic pathways such as arginine biosynthesis and the downregulation of mitochondrial proteins. Additionally, we observed markers of cellular stress induced by BPA by identifying multiple stress-induced proteins that were upregulated by this compound. As cellular processes affected by BPA have been shown to be evolutionarily conserved, these insights can advance our understanding of BPA's cellular impact and its broader effects on human health.