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Rhodosporidium toruloides-a new surrogate model to study rapamycin induced effects on human aging and cancer

Philipp M Cavelius1, Martina Haack1, Dania Awad1

  • 1Department of Chemistry, Werner Siemens-Chair of Synthetic Biotechnology, Technical University of Munich (TUM), Garching, Germany.

Cellular and Molecular Life Sciences : CMLS
|April 9, 2025
PubMed

Insights

Rhodosporidium toruloides yeast, a model for studying cellular lipid accumulation, shows differential responses to the Target of Rapamycin (TOR) inhibitor rapamycin between its two haplotypes, IFO0559 and IFO0880.

Area of Science:

  • Microbiology
  • Biochemistry
  • Cell Biology

Background:

  • Rhodosporidium toruloides is an oleaginous yeast known for accumulating lipids and carotenoids under stress.
  • Target of Rapamycin (TOR) signaling regulates cellular lipid accumulation and is crucial for cell proliferation.
  • R. toruloides possesses a single TOR kinase, unlike S. cerevisiae, making it a relevant model for mammalian systems.

Purpose of the Study:

  • To investigate the differential cellular response of two R. toruloides haplotypes (IFO0559 and IFO0880) to rapamycin treatment.
  • To analyze differences in lipid and carotenoid accumulation and proteomic profiles between haplotypes.
  • To evaluate R. toruloides as a model for studying rapamycin response in lipid-rich systems relevant to cancer and aging.

Main Methods:

  • Proteomics-centered approach.
  • Treatment of R. toruloides haplotypes IFO0559 and IFO0880 with the TOR inhibitor rapamycin.
  • Analysis of differential protein expression, lipid accumulation, and carotenoid production.

Main Results:

  • One haplotype (IFO0880) exhibited severe growth arrest upon rapamycin treatment, while the other (IFO0559) did not.
  • Proteomic analysis revealed differential expression of proteins involved in cell cycle control, lipogenesis, amino acid metabolism, and autophagy.
  • Identified proteins with known roles in mammalian oncogenesis and aging.

Conclusions:

  • R. toruloides exhibits haplotype-specific responses to rapamycin, highlighting the importance of genetic background.
  • The differential response suggests R. toruloides can serve as a valuable model for studying rapamycin's effects on lipid metabolism.
  • This yeast model is promising for investigating cellular mechanisms in cancer and age-related diseases characterized by high lipid content.
Keywords:
HaplotypesRapamycinRhodosporidiumTarget of rapamycinTime-resolved proteomics

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