The TORC1-Sch9-Rim15 signaling pathway represses yeast-to-hypha transition in response to glycerol availability in the oleaginous yeast Yarrowia lipolytica.

The yeast-to-hypha dimorphic transition is important for survival under nutrient starvation in fungi. The oleaginous yeast Yarrowia lipolytica grows in the oval-shaped yeast form in glycerol media whereas it adopts a filamentous form in glucose media. It is not clear why this yeast responds differently to glycerol and glucose. Here, we show that glycerol blocks dimorphic transition even in the presence of glucose whereas glycerol depletion induces filamentous growth, suggesting that dimorphic transition is repressed in response to glycerol availability. We show that the repression of dimorphic transition in glycerol media is mediated by the TORC1-Sch9 signaling pathway as both TORC1 inhibition and the loss of YlSch9 cause hyperfilamentation. TORC1-Sch9 signaling inhibits the nuclear translocation of YlRim15, a protein kinase that positively regulates filamentous growth, preventing it from entering the nucleus to activate the transcription of genes implicated in filamentous growth. Interestingly, TORC1-Sch9 signaling appears not to inhibit YlRim15 in glucose media, which could explain why Y. lipolytica responds differently to glycerol and glucose. We identified MHY1, a transcription factor-encoding gene known to be critical for filamentous growth, as one target regulated by the TORC1-Sch9-Rim15 signaling pathway. Our results provide new insights in the regulation of dimorphic transition in yeast.