Prion-dependent proteome remodeling in response to environmental stress is modulated by prion variant and genetic background

ABSTRACTA number of fungal proteins are capable of adopting multiple alternative, self-perpetuating prion conformations. These prion variants are associated with functional alterations of the prion-forming protein and thus the generation of new, heritable traits that can be detrimental or beneficial. Here we sought to determine the extent to which the previously-reported ZnCl2-sensitivity trait of yeast harboring the [PSI+] prion is modulated by genetic background and prion variant, and whether this trait is accompanied by prion-dependent proteomic changes that could illuminate its physiological basis. We also examined the degree to which prion variant and genetic background influence other prion-dependent phenotypes. We found that ZnCl2 exposure not only reduces colony growth but also limits chronological lifespan of [PSI+] relative to [psi−] cells. This reduction in viability was observed for multiple prion variants in both the S288C and W303 genetic backgrounds. Quantitative proteomic analysis revealed...