title: Differential proteome-metabolome profiling of YCA1-knock-out and wild type cells reveals novel metabolic pathways and cellular processes dependent on the yeast metacaspase.
abstract: The yeast Saccharomyces cerevisiae expresses one member of the metacaspase Cys protease family, encoded by the YCA1 gene. Combination of proteomics and metabolomics data showed that YCA1 deletion down-regulated glycolysis, the TCA cycle and alcoholic fermentation as compared with WT cells. Δyca1 cells also showed a down-regulation of the pentose phosphate pathway and 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 proteins 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 Δyca1 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 Δyca1 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 Δyca1 cells rather than a loss in pro-apoptotic YCA1-associated activity.
authors.affiliation: CNR, Istituto di Biomembrane e Bioenergetica, Via Amendola 165/a, 70126 Bari, Italy.
authors.forename: Maša
authors.initials: M
authors.lastname: Ždralević
authors.forename: Valentina
authors.initials: V
authors.lastname: Longo
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Guaragnella
authors.forename: Sergio
authors.initials: S
authors.lastname: Giannattasio
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Timperio
authors.forename: Lello
authors.initials: L
authors.lastname: Zolla
mesh_terms: D020169:Caspases / Q000235:genetics* / Q000378:metabolism; D055786:Gene Knockout Techniques; D055442:Metabolome / Q000235:genetics*; D055432:Metabolomics; D060066:Protein Interaction Maps / Q000235:genetics; D020543:Proteome / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; D020169:Caspases; C456272:MCA1 protein, S cerevisiae