New Yeast Model to Research How Rapamycin Affects Aging and Cancer

Jenn Hoskins
12th April, 2025

New Yeast Model to Research How Rapamycin Affects Aging and Cancer

Rapamycin treatment severely inhibited the growth of the Rhodosporidium toruloides IFO0880 haplotype while having little effect on the IFO0559 haplotype in nutrient-rich medium (a), demonstrating a key differential sensitivity that was absent in nutrient-poor medium (b).

Image adapted from: Cavelius et al. / CC BY (Source)

Key Findings

  • *In Germany, researchers examined two types of a special yeast to see how the drug rapamycin affects their growth and production of fats and pigments.*
  • *They discovered that one yeast type stopped growing when treated with rapamycin, while the other continued to grow, highlighting genetic differences in stress response.*
  • *The study also found protein changes in the yeasts similar to those in human cancers and aging, suggesting this yeast could help understand these human diseases.*
Rhodosporidium toruloides, a versatile oleaginous yeast, has garnered significant attention for its ability to produce valuable intracellular lipids and carotenoids, especially under metabolic stress[2]. These compounds are not only crucial for the yeast's survival but also hold potential for various biotechnological applications, including biofuels and nutraceuticals. Understanding the cellular mechanisms that regulate lipid and carotenoid accumulation in R. toruloides is essential for optimizing its use in industrial processes and for drawing parallels to similar processes in more complex organisms. A recent study conducted by researchers at the Technical University of Munich (TUM), Germany, delves into the role of the Target of Rapamycin (TOR) signaling pathway in R. toruloides[1]. The TOR pathway is a central regulator of cell growth and metabolism in eukaryotes, responding to nutrients, growth factors, and stress signals. In the well-studied yeast Saccharomyces cerevisiae, there are two TOR kinases, TOR1 and TOR2, which form distinct complexes known as TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2)[3]. These complexes have different roles, with TORC1 being sensitive to the drug rapamycin and primarily regulating growth, while TORC2 is involved in cytoskeletal organization and is insensitive to rapamycin. Unlike S. cerevisiae, R. toruloides possesses only a single TOR kinase, making its TOR signaling pathway more comparable to that of mammals, which also have a single TOR kinase. This similarity positions R. toruloides as a potentially valuable model for studying TOR-related processes relevant to human health, including cancer and age-related diseases characterized by altered lipid metabolism. In the TUM study, researchers focused on two haplotypes of R. toruloides, IFO0559 and IFO0880, examining their responses to rapamycin, a known inhibitor of TOR signaling. Using a proteomics-centered approach, the team analyzed how rapamycin treatment affected the accumulation of lipids and carotenoids in these yeast strains. Proteomics involves the large-scale study of proteins, providing insights into the functional aspects of the cell under different conditions. Unexpectedly, the two haplotypes exhibited markedly different responses to rapamycin. While IFO0880 experienced severe growth arrest upon treatment, IFO0559 did not show such a drastic effect. This divergence suggests underlying genetic or metabolic differences between the haplotypes that influence their sensitivity to TOR inhibition. Further proteomic analysis revealed that several proteins related to cell cycle control, lipogenesis (the process of lipid formation), amino acid metabolism, and autophagy (the cell's recycling process) were differentially expressed between the two haplotypes. Notably, some of the proteins identified in this study have been previously associated with oncogenic (cancer-related) and aging processes in mammals. This connection underscores the potential of R. toruloides as a surrogate model for investigating cellular mechanisms that are relevant to human diseases. By mimicking aspects of mammalian TOR signaling with its single TOR kinase, R. toruloides offers a simpler system to study complex processes without the redundancy seen in organisms like S. cerevisiae. The differential response observed between the haplotypes also builds upon earlier findings related to R. toruloides' adaptability to stress. For instance, previous research demonstrated that these yeast strains respond differently to copper-induced stress, affecting their lipid and carotenoid production[4]. The current study extends this understanding by showing that genetic factors governing TOR signaling can lead to varied metabolic outcomes under rapamycin treatment. Furthermore, the comprehensive proteomic approach used in the TUM study highlights the intricate network of proteins involved in managing cellular stress and maintaining lipid homeostasis. By identifying specific proteins that change in abundance in response to TOR inhibition, the research provides targets for genetic manipulation aimed at enhancing lipid production. This aligns with earlier advancements in genetic tools for R. toruloides, which have facilitated the engineering of strains with improved lipid and carotenoid yields[2]. In summary, the study from the Technical University of Munich illuminates the pivotal role of TOR signaling in regulating lipid and carotenoid accumulation in R. toruloides. By comparing the responses of two distinct haplotypes to rapamycin, the research not only advances our understanding of yeast metabolism but also establishes R. toruloides as a promising model for studying TOR-related pathways relevant to human health. This work bridges previous findings on yeast stress responses and genetic engineering, paving the way for future biotechnological innovations and insights into fundamental biological processes.

MedicineHealthBiotech

References

Main Study

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

Published 9th April, 2025

https://doi.org/10.1007/s00018-025-05662-4

Related Studies

2) Rhodosporidium toruloides - A potential red yeast chassis for lipids and beyond.

https://doi.org/10.1093/femsyr/foaa038

3) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control.

Journal: Molecular cell, Issue: Vol 10, Issue 3, Sep 2002

4) Adaptation of Proteome and Metabolism in Different Haplotypes of Rhodosporidium toruloides during Cu(I) and Cu(II) Stress.

https://doi.org/10.3390/microorganisms11030553


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