Proteome and metabolome profiling of wild-type and YCA1-knock-out yeast cells during acetic acid-induced programmed cell death.
Caspase proteases are responsible for the regulated disassembly of the cell into apoptotic bodies during mammalian apoptosis. Structural homologues of the caspase family (called metacaspases) are involved in programmed cell death in single-cell eukaryotes, yet the molecular mechanisms that contribute to death are currently undefined. Recent evidence revealed that a programmed cell death process is induced by acetic acid (AA-PCD) in Saccharomyces cerevisiae both in the presence and absence of metacaspase encoding gene YCA1. Here, we report an unexpected role for the yeast metacaspase in protein quality and metabolite control. By using an "omics" approach, we focused our attention on proteins and metabolites differentially modulated en route to AA-PCD either in wild type or YCA1-lacking cells. Quantitative proteomic and metabolomic analyses of wild type and Δyca1 cells identified significant alterations in carbohydrate catabolism, lipid metabolism, proteolysis and stress-response, highlighting the main roles of metacaspase in AA-PCD. Finally, deletion of YCA1 led to AA-PCD pathway through the activation of ceramides, whereas in the presence of the gene yeast cells underwent an AA-PCD pathway characterized by the shift of the main glycolytic pathway to the pentose phosphate pathway and a proteolytic mechanism to cope with oxidative stress.


CONCLUSIONS
The yeast metacaspase regulates both proteolytic activities through the ubiquitin-proteasome system and ceramide metabolism as revealed by proteome and metabolome profiling of YCA1-knock-out cells during acetic-acid induced programmed cell death.
Department of Ecology and Biology, "La Tuscia" University, Viterbo, Italy.
Valentina
V
Longo
Institute of Biomembrane and Bioenergetics, CNR, Bari, Italy.
Maša
M
Ždralević
Institute of Biomembrane and Bioenergetics, CNR, Bari, Italy.
Nicoletta
N
Guaragnella
Institute of Biomembrane and Bioenergetics, CNR, Bari, Italy.
Sergio
S
Giannattasio
Department of Ecology and Biology, "La Tuscia" University, Viterbo, Italy. Electronic address: zolla@unitus.it.
Lello
L
Zolla
Department of Ecology and Biology, "La Tuscia" University, Viterbo, Italy. Electronic address: timperio@unitus.it.
Anna Maria
AM
Timperio
D019342:Acetic Acid / Q000008:administration & dosage*; D020169:Caspases / Q000378:metabolism*; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D055786:Gene Knockout Techniques; D055442:Metabolome / Q000187:drug effects / Q000502:physiology; D020543:Proteome / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; D020169:Caspases; C456272:MCA1 protein, S cerevisiae; D019342:Acetic Acid
Acetic acid; Metabolomic; Metacaspase; Programmed cell death; Proteomic; Yeast