Crosstalk between RTG and TOR pathways mediates adaptation to amino acid starvation during fermentative growth in Saccharomyces cerevisiae.

One of the adaptations to this fermentative lifestyle is the retrograde pathway (RTG), which induces the transcription of genes, including several Krebs cycle genes, that 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 the levels of arginine 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 and improved their tolerance of canavanine. Relief of glucose repression via deletion of MIG1 restored RTG mutant growth under arginine limitation and improved canavanine tolerance in some but not all RTG mutants. rtg2Delta mutants exhibited more canavanine sensitivity than other RTG mutants and was not rescued by mig1Delta, suggesting that this gene has an another role in addition to being a chaperone of the Rtg1/3 complex.