Here the anti-fungal mechanism of GSE induced apoptosis was studied in yeast cells, which is an ideal model organism to investigate various aspects of mitochondrial biology. Laun and colleagues used global transcriptome analysis to investigate the mechanism underlying the apoptotic phenotype of S. cerevisiae using temperature-sensitive Dcdc48S565G cells. The genes involved in cell-cycle regulation, DNA repair, oxidative stress response, mitochondrial functions and cell-surface rearrangement were differentially regulated during yeast apoptosis. However, in mammalian cells, a large fraction of the events guiding cell death programs are dependent on protein post-translational modification rather than on genomic regulatory pathways. Therefore, the functional characterization of proteins and regulatory networks involved in these processes is essential to further elucidate apoptosis as a mechanistic phenomenon. Metabolic fluxes constitute a fundamental determination of cell physiology because they provide a Guanethidine Sulfate measure of the degree of engagement of various pathways in overall cellular functions and metabolic processes. Metabonomics and proteomics were firstly used together to investigate the yeast apoptosis mediated by mitochondria-dependent pathway. In the present article, we provided evidence that GSE-induced cell death exhibited features in common with apoptosis. Metabonomics and proteomics analysis revealed that the cells initially resisted dying and why they eventually, and irreversibly, committed suicide. The region was excluded prior to statistical analysis to remove the variation in water suppression efficiency. All remaining regions of the spectra were scaled to the total integrated area of the spectra to reduce any significant concentration differences. The data set was mean centered prior to PCA and PLS-DA processing. First, to discern the presence of inherent similarities of spectral profiles, an unsupervised pattern recognition method, PCA, was conducted for the cell extracts samples. GSE is a natural rich source of the polyphenols. The polyphenols in the GSE were often measured as gallic acid equivalent. Gallic acid was identified as the major activity component of GSE in many articles. GSE exerted potent antifungal activity against the yeast-like fungi strains and lower activity against dermatophytes and molds. In another PYR-41 experiment Ignacio and Thai demonstrated that GSE is as effective as miconazole nitrate salt. In this study we found 0.13 mg/mL GSE could inhibit the yeast effectively, which is coincident with. As no one had reported why GSE could kill the fungi. Then it is helpful to study the inhibitory mechanism for better understanding of this fungicide. Severin and colleagues elegantly extended their findings towards a timeline of events, proposing a scheme of the mitochondrial death cascade in yeast. In summary, treatment of yeast cells with a-factor or amiodarone leads to hyperpolarisation of the mitochondrial membrane potential DYmt. Elevation of DYmt promotes ROS production, which then initiates the mitochondrial thread-grain transition and deenergisation. The mitochondrial de-energisation finally results in loss of DYmt. DYmt and ROS changes in our study were consistent with Pozniakovsky et al. and Severin et al.. Proline is a water-soluble amino acid that prevents cell death from dehydration under osmotic stress and increased the performance of yeast against GSE. The pantothenic acid content increased because its conversion to CoA was blocked. Without CoA, pyruvic acid could not enter into the citric acid cycle, which was consistent with reduction of CIT1 and PDB1.