Protein kinase A and Sch9 cooperatively regulate induction of autophagy in Saccharomyces cerevisiae

Autophagy is a conserved degradative pathway in eukaryotic cells, tightly regulated by nutrient-sensing mechanisms. While the rapamycin-sensitive Target of Rapamycin Complex 1 (TORC1) is known to play a key role in autophagy induction, the full scope of its regulation remains incompletely understood. In this study, we demonstrate that the protein kinase A (PKA) and Sch9 1-Naphthyl PP1 signaling pathways cooperatively regulate autophagy in yeast. Autophagy is robustly induced when both PKA and Sch9 are simultaneously inactivated. Using mutant alleles of PKA and Sch9 that are sensitive to the ATP-analogue inhibitor C3-1′-naphthyl-methyl PP1, we show that autophagy activation occurs independently of TORC1 activity. This PKA-Sch9-dependent autophagy pathway requires the autophagy-related kinase Atg1 complex—also essential in TORC1-mediated autophagy—as well as the transcription factors Msn2/4 and the kinase Rim15. These findings indicate that autophagy in yeast is regulated by signals from at least three distinct but partially overlapping nutrient-sensing pathways: PKA, Sch9, and TORC1.