The interplay of nutrient signalling, pH homeostasis and inter-organelle communication as key factor for cellular ageing and longevity

The highly conserved TORC1 signalling pathway has been proven to be important in the regulation of lifespan in many organism. Via its downstream effector Sch9, the orthologue of mammalian Akt/PKB and S6K1, it affects various cellular processes including translation, induction of stress response gene expression and metabolism, in this way impacting on cellular ageing and lifespan. Nevertheless, Sch9 acts as an integrator of many different nutritional stimuli that are believed to affect its activity and target specificity. Previous research already demonstrated that Sch9 is not only phosphorylated by TORC1 in response to nitrogen, it also receives input about glucose availability and lipid homeostasis. Based on the already described genetic interaction between the phosphate signalling kinase Pho85 and Sch9 and their previously shown convergence on the transcriptional regulator Rim15, we aim to unravel the interplay between these two pathways. The second goal of this PhD project is the identification of new functions and targets of TORC1 and Sch9. Based on the previously described nutritional inputs on these kinases and the already identified effectors, several potential TORC1-Sch9 regulated processes will be further investigated, including phosphate metabolism, vacuolar amino acid homeostasis, nitrogen-dependent pH homeostasis, interorganelle communication, lipid homeostasis and acetic acid metabolism. Finally, we want to provide insights in how these newly identified functions contribute to the determination of cellular lifespan.

Jaar van publicatie:2021

Toegankelijkheid:Open