Comprehensive analysis of the proteome of S. cerevisiae wild-type and pdr5 cells in response to Bisphenol A (BPA) exposure

Bisphenol A, an endocrine-disrupting compound, is used widely 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 proteome changes of wild-type and PDR5-deleted S. cerevisiae strains exposed to different doses of BPA using sample multiplexing-based quantitative mass spectrometry. We found that the ABC multidrug transporter Pdr5 plays an important role in protecting yeast cells from BPA toxicity, with its absence significantly sensitizes 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 dose-dependent widespread changes in protein abundance, including the up-regulation of metabolic pathways such as arginine biosynthesis and the down-regulation of mitochondrial proteins. Additionally, we observed markers of cellular stress induced by BPA by identifying multiple stress-induced proteins up-regulated by this compound. As cellular processes affected by BPA have been shown to be evolutionary conserved, these insights can advance our understanding of BPA’s cellular impact and its broader effects on human health.