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A yeast prion, Mod5, promotes acquired drug resistance and cell survival under environmental stress

Genjiro Suzuki1, Naoyuki Shimazu, Motomasa Tanaka

  • 1Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Science (New York, N.Y.)
|April 21, 2012
PubMed

Insights

Yeast cells can adapt to antifungal drugs by converting the Mod5 protein into a prion. This prion formation regulates cellular pathways, enhancing survival under environmental stress and demonstrating active prion roles in adaptation.

Area of Science:

  • Cellular biology
  • Biochemistry
  • Yeast genetics

Background:

  • Prion proteins convert from soluble to aggregated states, potentially aiding cellular adaptation.
  • The role of active prion conversion in conferring fitness advantages under environmental stress is not well understood.

Purpose of the Study:

  • To investigate if yeast cells actively use prion conversion for environmental adaptation.
  • To identify specific prion proteins involved in stress response and their mechanisms.

Main Methods:

  • Identification of Mod5, a yeast transfer RNA isopentenyltransferase, as a prion protein.
  • Analysis of Mod5 prion conversion's effect on cellular pathways, specifically sterol biosynthesis.
  • Experimental exposure of yeast to antifungal drugs to observe prion formation and survival rates.

Main Results:

  • Mod5 prion conversion was found to regulate the sterol biosynthetic pathway.
  • This regulation conferred acquired cellular resistance against antifungal agents in yeast.
  • Antifungal drug selective pressure promoted the de novo appearance of Mod5 prion states, enhancing cell survival.

Conclusions:

  • Active prion conversion, exemplified by Mod5, can actively contribute to cellular adaptation in response to environmental challenges.
  • Phenotypic changes driven by prion formation under selective pressure are a mechanism for survival in organisms.
  • Prion-mediated regulation of metabolic pathways offers a novel perspective on evolutionary adaptation.

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