Carleton Univ, Dept Biol, 1125 Colonel By Dr, Ottawa, ON K1S 5B6 - Canada
 Carleton Univ, Ottawa Inst Syst Biol, 1125 Colonel By Dr, Ottawa, ON K1S 5B6 - Canada
 Univ Fed Sao Paulo, Dept Quim, Lab Bioinorgan & Toxicol Ambiental LABITA, Rua Prof Artur Riedel 275, BR-09972270 Diadema, SP - Brazil
Total Affiliations: 3
APR 25 2019.
Web of Science Citations:
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 Mn2+ exert on eukaryotic cell biology, we exposed a non-essential deletion library of the yeast Saccharomyces cerevisiae to a sub-inhibitory concentration of Mn2+ 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 beta-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. (AU)