Sulfur sparing in the yeast proteome in response to sulfur demand.
Genome-wide studies have recently revealed the unexpected complexity of the genetic response to apparently simple physiological changes. Here, we show that when yeast cells are exposed to Cd(2+), most of the sulfur assimilated by the cells is converted into glutathione, a thiol-metabolite essential for detoxification. Cells adapt to this vital metabolite requirement by modifying globally their proteome to reduce the production of abundant sulfur-rich proteins. In particular, some abundant glycolytic enzymes are replaced by sulfur-depleted isozymes. This global change in protein expression allows an overall sulfur amino acid saving of 30%. This proteomic adaptation is essentially regulated at the mRNA level. The main transcriptional activator of the sulfate assimilation pathway, Met4p, plays an essential role in this sulfur-sparing response.
Fauchon
Mirène
M
Service de Biochimie et Génétique Moléculaire, Bâtiment 142, CEA/Saclay, F-91191 Gif-sur-Yvette Cedex, France.
Lagniel
Gilles
G
Aude
Jean Christophe
JC
Lombardia
Luis
L
Soularue
Pascal
P
Petat
Cyrille
C
Marguerie
Gérard
G
Sentenac
André
A
Werner
Michel
M
Labarre
Jean
J
D000222:Adaptation, Physiological / Q000235:genetics; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors; D002104:Cadmium / Q000494:pharmacology*; D003545:Cysteine / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005978:Glutathione / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008715:Methionine / Q000378:metabolism; D020543:Proteome; D011767:Pyruvate Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D012331:RNA, Fungal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013455:Sulfur / Q000378:metabolism*; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D007527:Isoenzymes; C073675:MET4 protein, S cerevisiae; D020543:Proteome; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D002104:Cadmium; D013455:Sulfur; D008715:Methionine; D000444:Aldehyde Dehydrogenase; D011767:Pyruvate Decarboxylase; D005978:Glutathione; D003545:Cysteine