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

## TL;DR

This study explores how the yeast Rhodosporidium toruloides responds to rapamycin, a drug linked to aging and cancer, and finds differences between two strains that could help understand human disease.

## Contribution

The study introduces Rhodosporidium toruloides as a novel single-TOR surrogate model for studying rapamycin effects, relevant to human aging and cancer.

## Key findings

- One R. toruloides strain showed severe growth arrest with rapamycin, while another did not.
- Proteomic analysis revealed differences in cell cycle, lipid metabolism, and autophagy proteins between the two strains.
- Some identified proteins are linked to mammalian cancer and aging processes.

## Abstract

The haploid, olegenious yeast Rhodosporidium toruloides accumulates intracellular lipids and carotenoids upon metabolic stress. Target of Rapamycin (TOR) signaling, essential for cell proliferation, is known to affect cellular lipid accumulation. In contrast to the conventional surrugate cell model S. cerevisiae, which harbours two TOR kinases within its TOR complex, R. toruloides only harbours one TOR kinase, mimicking mammalian systems. We used a proteomics centered approach to probe the cellular response, of the two R. toruloides haplotypes, IFO0559 and IFO0880 upon treatment with the TOR inhibitor rapamycin, with an original focus on difference in carotenoid and lipid accumulation. Unexpectedly, IFO0880 displayed severe growth arrest in response to rapamycin, while IFO0559 did not. Proteomic anaysis revealed differential expression of several proteins involved in cell cycle control, lipogensis, amino acid metabolism and autophagy between the two haplotypes. Among those we identified several proteins previously described in both mammalian oncogenic and aging contexts. This differential haplotype response to rapamycin treatment positions R. toruloides as a promising cell surrugate model to study cellular mechanisms underlying rapamycin response especially for systems with high lipid contents, an emerging hallmark of different forms of mammalian cancer and age related disease.

The online version contains supplementary material available at 10.1007/s00018-025-05662-4.