Cooperative Function of Atg8- and TORC1-Mediated Activities in Yeast.

The target of rapamycin complex 1 (TORC1) protein kinase plays an important role in regulating various cellular activities in response to nutrient availability. In this study, an autophagy-related protein 8 (atg8) mutant of Saccharomyces cerevisiae was highly sensitive to cellular processes in which TORC1 activity was inhibited by rapamycin treatment or by a mutated allele of KOG1 which encodes a subunit of TORC1. Atg8 exhibits both lipidation-dependent and -independent activities, each involving distinct factors. Lipidation of Atg8 is necessary for autophagy and functions with autophagy-related proteins like Atg7, whereas the lipidation-independent activities of Atg8 require Hfl1. The atg7Δhfl1Δ double mutant exhibited defects for the impaired TORC1 activities, suggesting that both lipidation-dependent and -independent functions of Atg8 are required for survival during impaired TORC1 activity. Moreover, atg8Δ and atg7Δhfl1Δ mutants exhibited sensitivity to metal ion Zn²⁺ during low-dose rapamycin treatment. The results suggest that Atg8-mediated functions and TORC1 signaling events play an important role in cell growth, possibly by maintaining vacuole integrity.