Zinc oxide nanoparticles impose metabolic toxicity by de-regulating proteome and metabolome in Saccharomyces cerevisiae

As zinc oxide nanoparticles are being increasingly used in various applications, it is important to assess their potential toxic implications. Stress responses and adaptations are primarily controlled by modulation in cellular proteins (enzyme) and concentration of metabolites. To date proteomics or metabolomics applications in nanotoxicity assessment have been applied to a restricted extent. Here we utilized 2DE and H-1 NMR based proteomics and metabolomics respectively to delineate the toxicity mechanism of zinc oxide nanoparticles (ZnONPs) in budding yeast S. cerevisiae. We found that the physiological and metabolic processes were altered in the S. cerevisiae upon ZnO-NPs exposure. Almost 40% proteins were down-regulated in ZnO-NPs (10 mg L-1) exposed cell as compared to control. Metabolomics and system biology based pathway analysis, revealed that ZnO-NPs repressed a wide range of key metabolites involved in central carbon metabolism, cofactors synthesis, amino acid and fatty acid biosynthesis, purines and pyrimidines, nucleoside and nucleotide biosynthetic pathways. These metabolic changes may be associated with the energy metabolism, antioxidation, DNA and protein damage and membrane stability. We concluded that untargeted proteomic and metabolic approaches provide more complete measurements and suggest probable molecular mechanisms of nanomaterials toxicity.