Crosstalk between RTG and TOR pathways mediates adaptation to amino acid starvation during fermentative growth in Saccharomyces cerevisiae
- 1Department of Plant Pathology and Microbiology, The Institute of Environmental Sciences, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University , 229 Herzl St., Rehovot 7610001 ,
- 2Shmunis School of Biomedical and Cancer Research, Tel Aviv University , 55 Levanon St., Tel Aviv 6997801 ,
Abstract
In the presence of glucose, Saccharomyces cerevisiae prefers glycolysis followed by fermentation to generate ATP. One adaptation to this fermentative lifestyle is the retrograde pathway (RTG), which induces the transcription of genes, including several Krebs cycle genes, to increase pools of alpha-ketoglutarate. We previously found that both petite and RTG mutants are highly sensitive to canavanine, a toxic analog of arginine, indicating that residual respiration and the RTG pathway are required to maintain arginine levels in the cell. Yet, from an amino acid biosynthesis standpoint, it is unclear how the RTG pathway balances between respiration and fermentation. Here, we show that use of a non-fermentable carbon source restored RTG mutants’ ability to grow without arginine or lysine and improved their growth on canavanine and thialysine. Relief of glucose repression via deletion of MIG1 improved RTG mutant growth on agar under arginine or lysine limitation but was not sufficient to restore growth on a toxic analog. rtg2Δ exhibited more canavanine sensitivity than other RTG mutants, was not rescued by mig1Δ, and was only partially rescued by mks1Δ, suggesting that Rtg2 may have an additional function required for canavanine tolerance. Target of rapamycin (TOR) signaling as a pro-growth factor suppresses the RTG pathway, but it is unknown if both pathways complement each other. We found that TOR signaling contributes to canavanine tolerance in an RTG-independent manner. The broad implications of our results are found in the importance of fermentative lifestyle under amino acid starvation as part of industrial and malignant ecosystems.
Related
- Adaptation of fluorescence rescue reporters of mistranslation for use in Saccharomyces cerevisiae
- Scp160 deletion suppresses TDP-43 aggregation and toxicity in Saccharomyces cerevisiae
- Chemogenomic profiling of diverse Saccharomyces cerevisiae strains using the novel CRISPR-Cas9 markerless barcoded library BarMix
- The Linker Histone Plays a Dual Role during Gametogenesis in Saccharomyces cerevisiae
- Engineered protein degradation of farnesyl pyrophosphate synthase is an effective regulatory mechanism to increase monoterpene production in Saccharomyces cerevisiae
BibTeX
@article{druseikis2026crosstalk,
title = {{Crosstalk between RTG and TOR pathways mediates adaptation to amino acid starvation during fermentative growth in Saccharomyces cerevisiae}},
author = {Marina Druseikis and Shay Covo},
journal = {G3: Genes, Genomes, Genetics},
year = {2026},
month = oct,
doi = {10.1093/g3journal/jkag261},
url = {https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkag261/8971170},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Crosstalk between RTG and TOR pathways mediates adaptation to amino acid starvation during fermentative growth in Saccharomyces cerevisiae
AU - Marina Druseikis
AU - Shay Covo
PY - 2026
DA - 2026/10/22
JO - G3: Genes, Genomes, Genetics
DO - 10.1093/g3journal/jkag261
UR - https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkag261/8971170
AB - In the presence of glucose, Saccharomyces cerevisiae prefers glycolysis followed by fermentation to generate ATP. One adaptation to this fermentative lifestyle is the retrograde pathway (RTG), which induces the transcription of genes, including several Krebs cycle genes, to increase pools of alpha-ketoglutarate. We previously found that both petite and RTG mutants are highly sensitive to canavanine, a toxic analog of arginine, indicating that residual respiration and the RTG pathway are required to maintain arginine levels in the cell. Yet, from an amino acid biosynthesis standpoint, it is unclear how the RTG pathway balances between respiration and fermentation. Here, we show that use of a non-fermentable carbon source restored RTG mutants’ ability to grow without arginine or lysine and improved their growth on canavanine and thialysine. Relief of glucose repression via deletion of MIG1 improved RTG mutant growth on agar under arginine or lysine limitation but was not sufficient to restore growth on a toxic analog. rtg2Δ exhibited more canavanine sensitivity than other RTG mutants, was not rescued by mig1Δ, and was only partially rescued by mks1Δ, suggesting that Rtg2 may have an additional function required for canavanine tolerance. Target of rapamycin (TOR) signaling as a pro-growth factor suppresses the RTG pathway, but it is unknown if both pathways complement each other. We found that TOR signaling contributes to canavanine tolerance in an RTG-independent manner. The broad implications of our results are found in the importance of fermentative lifestyle under amino acid starvation as part of industrial and malignant ecosystems.
SN - 2160-1836
ER -