Manganese-induced cellular disturbance in the baker’s yeast, Saccharomyces cerevisiae with putative implications in neuronal dysfunction
Scientific Reports , Volume 9 - Issue 1
Manganese (Mn) is an essential element, but in humans, chronic and/or acute exposure to this metal can lead to neurotoxicity and neurodegenerative disorders including Parkinsonism and Parkinson’s Disease by unclear mechanisms. To better understand the effects that exposure to Mn 2+ exert on eukaryotic cell biology, we exposed a non-essential deletion library of the yeast Saccharomyces cerevisiae to a sub-inhibitory concentration of Mn 2+ followed by targeted functional analyses of the positive hits. This screen produced a set of 43 sensitive deletion mutants that were enriched for genes associated with protein biosynthesis. Our follow-up investigations demonstrated that Mn reduced total rRNA levels in a dose-dependent manner and decreased expression of a β-galactosidase reporter gene. This was subsequently supported by analysis of ribosome profiles that suggested Mn-induced toxicity was associated with a reduction in formation of active ribosomes on the mRNAs. Altogether, these findings contribute to the current understanding of the mechanism of Mn-triggered cytotoxicity. Lastly, using the Comparative Toxicogenomic Database, we revealed that Mn shared certain similarities in toxicological mechanisms with neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer’s, Parkinson’s and Huntington’s diseases.
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Hernández, R.B. (Raúl Bonne), Moteshareie, H. (Houman), Burnside, D. (Daniel), McKay, B, & Golshani, A. (2019). Manganese-induced cellular disturbance in the baker’s yeast, Saccharomyces cerevisiae with putative implications in neuronal dysfunction. Scientific Reports, 9(1). doi:10.1038/s41598-019-42907-2