Differential proteome-metabolome profiling of YCA1-knock-out and wild type cells reveals novel metabolic pathways and cellular processes dependent on the yeast metacaspase.

The yeast Saccharomyces cerevisiae expresses one member of metacaspase Cys protease family, encoded by YCA1 gene. Combination of proteomics and metabolomics data showed YCA1 deletion down-regulated glycolysis, TCA cycle and alcoholic fermentation as compared with WT cells. ?yca1 cells also showed a down-regulation of the pentose phosphate pathway and an accumulation of pyruvate, correlated with higher levels of certain amino acids found in these cells. Accordingly, there is a decrease in protein biosynthesis, and up-regulation of specific stress response protein like Ahp1p, which possibly provides these cells with a better protection against stress. Moreover, in agreement with the down-regulation of protein biosynthesis machinery in ?yca1 cells, we have found that regulation of transcription, co-translational protein folding and protein targeting to different subcellular locations were also down-regulated. Metabolomics analysis of the nucleotide content showed a significant reduction in ?yca1 cells in comparison with the WT, except for GTP content which remained unchanged. Thus, our combined proteome/metabolome approach added a new dimension to the non-apoptotic function of yeast metacaspase, which can specifically affect cell metabolism through as yet unknown mechanisms and possibly stress-response pathways, like HOG and cell wall integrity pathways. Certainly, YCA1 deletion may induce compensatory changes in stress response proteins offering a better protection against apoptosis to ?yca1 cells rather than a loss in a pro-apoptotic YCA1- associated activity.