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Vmr 1p is a novel vacuolar multidrug resistance ABC transporter in Saccharomyces cerevisiae

Donata Wawrzycka1, Iwona Sobczak, Grzegorz Bartosz

  • 1Genetics and Microbiology Institute, Wrocław University, Wrocław, Poland.

FEMS Yeast Research
|September 18, 2010
PubMed

Insights

The Saccharomyces cerevisiae Yhl035p/Vmr1p (Vmr1p) transporter is crucial for drug and metal resistance. Deleting the YHL035 gene increases sensitivity to toxic substances, highlighting Vmr1p's role in cellular protection.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cell Biology

Background:

  • The Saccharomyces cerevisiae Yhl035p/Vmr1p is an ABC transporter belonging to the MRP subfamily.
  • This transporter is conserved across all post Whole Genome Duplication species.

Purpose of the Study:

  • To investigate the function of the Yhl035p/Vmr1p transporter in Saccharomyces cerevisiae.
  • To determine the role of Vmr1p in cellular resistance to amphiphilic drugs and toxic metals.

Main Methods:

  • Gene deletion analysis of YHL035.
  • Localization studies using Vmr1p-GFP.
  • Vesicular transport assays.
  • Growth sensitivity assays under different media conditions.

Main Results:

  • Deletion of YHL035 resulted in growth sensitivity to amphiphilic drugs (cycloheximide, 2,4-dichlorophenoxyacetic acid, 2,4-dinitrophenol) and toxic metals (cadmium).
  • Vmr1p localizes to the vacuolar membrane.
  • ATP-dependent transport of DNP-S-glutathione conjugate was reduced in VMR1 deletants.
  • Energy-dependent efflux of rhodamine 6G was increased in VMR1 deletants.
  • Cadmium sensitivity was more pronounced in glycerol/ethanol-grown cells compared to glucose-grown cells.
  • VMR1 promoter activity was higher in glycerol/ethanol and activated by ADR1 deletion in glucose.

Conclusions:

  • Saccharomyces cerevisiae Yhl035p/Vmr1p is an essential transporter involved in the efflux of various toxic compounds.
  • Vmr1p plays a significant role in cellular defense mechanisms against amphiphilic drugs and heavy metals.
  • Environmental conditions and regulatory factors like ADR1 influence VMR1 expression and function.

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