Manganese Could Indirectly Promote Generation and Propagation of the Yeast Prion URE3 and Increase Molecular Chaperones Expression in Budding Yeast

Prion diseases are caused by self-propagating and transmissible alternative conformations of certain proteins, which induce neurotoxicity and lead to transmissible spongiform encephalopathy (TSE) in mammalian. Prions were also found in fungi, and in particular, the yeast Saccharomyces cerevisiae. Manganese (Mn) is an essential nutrient and plays crucial roles in central nervous system. However, high concentration of manganese is regarded as an environmental neuronal stressor which would induce striatal neurotoxicity. Long-term exposure to high concentration of manganese would increase the proportion of the infectiously pathogenic isoform (PrPSc) of prion protein. Additionally, increase of manganese levels was found to be age-related in human brain. Here, we studied the effect of manganese on prion using budding yeast prion URE3 as model organism. We found the exposure to manganese can enhance the de novo generation and propagation of yeast prion URE3, as well as the expression levels of chaperones Hsp104p and Hsp70p, in a dose-dependent manner.