The Toxic Effects of Tetrachlorobisphenol A in Saccharomyces cerevisiae Cells via Metabolic Interference

Tetrachlorobisphenol A (TCBPA) is a common flame retardant detected in different environments. However, its toxic effects on animals and humans are not fully understood. Here, the differential intracellular metabolites and associated gene expression were used to clarify the metabolic interference of TCBPA in Saccharomyces cerevisiae, a simple eukaryotic model organism. The results indicated that TCBPA treatment promoted the glycolysis pathway but inhibited the tricarboxylic acid (TCA) cycle, energy metabolism and the hexose monophosphate pathway (HMP) pathway. Thus, the HMP pathway produced less reducing power, leading to the accumulation of reactive oxygen species (ROS) and aggravation of oxidative damage. Accordingly, the carbon flux was channelled into the accumulation of fatty acids, amino acids and glycerol instead of biomass production and energy metabolism. The accumulation of these metabolites might serve a protective function against TCBPA stress by maintaining the cell membrane integrity or providing a stable intracellular environment in S. cerevisiae. These results enhance our knowledge of the toxic effects of TCBPA on S. cerevisiae via metabolic interference and pave the way for clarification of the mechanisms underlying TCBPA toxicity in animals and humans.