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

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Abstract

The yeast Saccharomyces cerevisiae expresses one member of metacaspase Cys protease family,encoded by YCA1 gene. Combination of proteomics and metabolomics data showed YCA1deletion down-regulated glycolysis, TCA cycle and alcoholic fermentation as compared with WTcells. ?yca1 cells also showed a down-regulation of the pentose phosphate pathway and anaccumulation of pyruvate, correlated with higher levels of certain amino acids found in thesecells. Accordingly, there is a decrease in protein biosynthesis, and up-regulation of specific stressresponse protein like Ahp1p, which possibly provides these cells with a better protection againststress. 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 andprotein targeting to different subcellular locations were also down-regulated.Metabolomics analysis of the nucleotide content showed a significant reduction in ?yca1 cells incomparison with the WT, except for GTP content which remained unchanged. Thus, ourcombined proteome/metabolome approach added a new dimension to the non-apoptotic functionof yeast metacaspase, which can specifically affect cell metabolism through as yet unknownmechanisms and possibly stress-response pathways, like HOG and cell wall integrity pathways.Certainly, YCA1 deletion may induce compensatory changes in stress response proteins offering abetter protection against apoptosis to ?yca1 cells rather than a loss in a pro-apoptotic YCA1-associated activity.

Autore Pugliese

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  • Zdralevic M.; Longo V.; Guaragnella N.; Giannattasio S.; Timperio A.M.; Zolla L.

Titolo volume/Rivista

Molecular bioSystems

Anno di pubblicazione

2015

ISSN

1742-206X

ISBN

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