Sulfur sparing in the yeast proteome in response to sulfur demand

Mol Cell. 2002 Apr;9(4):713-23. doi: 10.1016/s1097-2765(02)00500-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics
  • Aldehyde Dehydrogenase / biosynthesis
  • Aldehyde Dehydrogenase / genetics
  • Basic-Leucine Zipper Transcription Factors
  • Cadmium / pharmacology*
  • Cysteine / metabolism
  • DNA-Binding Proteins / physiology*
  • Electrophoresis, Gel, Two-Dimensional
  • Gene Expression Regulation, Fungal / drug effects*
  • Glutathione / biosynthesis*
  • Glutathione / genetics
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Isoenzymes / physiology*
  • Methionine / metabolism
  • Proteome*
  • Pyruvate Decarboxylase / biosynthesis
  • Pyruvate Decarboxylase / genetics
  • RNA, Fungal / metabolism
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / biosynthesis
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*
  • Sulfur / metabolism*
  • Trans-Activators / physiology*
  • Transcription, Genetic / drug effects

Substances

  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Isoenzymes
  • MET4 protein, S cerevisiae
  • Proteome
  • RNA, Fungal
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Cadmium
  • Sulfur
  • Methionine
  • Aldehyde Dehydrogenase
  • Pyruvate Decarboxylase
  • Glutathione
  • Cysteine