ERG6 and PDR5 regulate small lipophilic drug accumulation in yeast cells via distinct mechanisms

Roger Emter, Antje Heese-Peck, Anastasia Kralli

Research output: Contribution to journalArticlepeer-review

Abstract

Diagnosis and circumvention of multi-drug resistance requires an understanding of the underlying cellular mechanisms. In the model organism Saccharomyces cerevisiae, deletions of PDR5 or ERG6 increase sensitivity to many small lipophilic drugs. Pdr5p is a plasma membrane ATP-binding cassette transporter that actively exports drugs, thereby lowering their intracellular levels. The mechanism by which ERG6, an enzyme in sterol biosynthesis, affects drug accumulation is less clear. We show here that ERG6 limits the rate of passive drug diffusion across the membrane, without affecting Pdr5p-mediated drug export. Consistent with their action by distinct mechanisms, PDR5 and ERG6 effects on drug accumulation are additive.

Original languageEnglish (US)
Pages (from-to)57-61
Number of pages5
JournalFEBS Letters
Volume521
Issue number1-3
DOIs
StatePublished - Jun 19 2002
Externally publishedYes

Keywords

  • ATP-binding cassette transporter
  • Drug resistance
  • Small lipophilic molecule transport
  • Sterol
  • Yeast

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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