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Penetrating cations induce pleiotropic drug resistance in yeast

Kseniia V Galkina1, Elizaveta G Besedina1, Roman A Zinovkin2,3,4

  • 1Faculty of Bioengineering and Bioinformatics, Moscow State University, Leninskiye Gory 1-73, Moscow, 119991, Russia.

Scientific Reports
|May 27, 2018
PubMed

Insights

Lipophilic cations, like dodecyltriphenylphosphonium (C12TPP), can activate pleiotropic drug resistance (PDR) transporter gene expression in yeast. This activation occurs independently of mitochondrial signaling pathways.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Yeast Genetics

Background:

  • Pleiotropic drug resistance (PDR) transporters mediate drug efflux.
  • Substrate binding to transcription factors typically induces PDR transporter gene expression.
  • The role of penetrating cations in PDR activation is unclear due to potential mitochondrial sequestration.

Purpose of the Study:

  • To investigate the effect of penetrating cations on PDR activation in Saccharomyces cerevisiae.
  • To determine if mitochondrial sequestration inhibits PDR activation by lipophilic cations.
  • To elucidate the signaling pathways involved in cation-induced PDR gene expression.

Main Methods:

  • Utilized Saccharomyces cerevisiae as a model organism.
  • Assessed the impact of dodecyltriphenylphosphonium (C12TPP) on PDR gene expression (PDR5, SNQ2, YOR1).
  • Quantified PDR transporter protein levels and substrate accumulation.
  • Investigated the roles of transcription factors PDR1 and PDR3.
  • Examined the involvement of mitochondrial signaling pathways (YAP1, RTG2).

Main Results:

  • The lipophilic cation C12TPP induced the expression of PDR transporter genes PDR5, SNQ2, and YOR1.
  • C12TPP treatment increased Pdr5p and Snq2p protein levels and reduced Nile red accumulation.
  • PDR1 was essential for C12TPP-induced gene expression, while PDR3 was not required.
  • Mitochondrial signaling pathway components YAP1 and RTG2 were dispensable for the observed C12TPP effects.

Conclusions:

  • Mitochondrial sequestration of lipophilic cations does not significantly impede PDR activation.
  • The induction of PDR transporter genes by lipophilic cations does not necessitate mitochondria as a signaling module.
  • PDR gene activation by penetrating cations is mediated by transcription factors like PDR1, independent of mitochondrial pathways.

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