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Updated: Jul 31, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Manganese-induced cellular disturbance in the baker's yeast, Saccharomyces cerevisiae with putative implications in
Raúl Bonne Hernández1,2, Houman Moteshareie3, Daniel Burnside3
1University Federal de São Paulo Departamento de Química, Laboratorio de Bioinorgânica e Toxicologia Ambiental - LABITA, Rua Prof. Artur Riedel, 275, CEP: 09972-270, Diadema, SP, Brazil. rbhernandez@unifesp.br.
Abstract:
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 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.
Insights
Manganese (Mn) exposure harms eukaryotic cells by disrupting protein synthesis and reducing ribosome activity. This research sheds light on Mn-triggered neurotoxicity and its links to neurodegenerative diseases.
Area of Science:
- Cell Biology
- Toxicology
- Neuroscience
Background:
- Manganese (Mn) is essential but toxic at high levels, causing neurotoxicity and neurodegenerative disorders.
- Mechanisms of Mn-induced neurotoxicity, particularly its cellular effects, remain unclear.
- Understanding Mn's impact on eukaryotic cell biology is crucial for addressing associated health risks.
Purpose of the Study:
- To investigate the cellular effects of manganese (Mn2+) exposure in Saccharomyces cerevisiae.
- To identify genes and pathways affected by Mn2+ exposure using a deletion library screen.
- To elucidate the mechanisms underlying Mn-induced cytotoxicity and its connection to neurodegenerative diseases.
Main Methods:
- A non-essential deletion library of Saccharomyces cerevisiae was exposed to sub-inhibitory concentrations of Mn2+.
- Functional analyses were performed on sensitive deletion mutants identified in the screen.
- Ribosome profiling and reporter gene assays were used to assess Mn's impact on protein synthesis.
- The Comparative Toxicogenomic Database was utilized to compare Mn's toxicological profile with neurodegenerative disorders.
Main Results:
- A screen identified 43 sensitive deletion mutants, enriched for genes involved in protein biosynthesis.
- Mn exposure reduced total rRNA levels in a dose-dependent manner.
- Mn decreased reporter gene expression and ribosome profiles indicated reduced active ribosome formation on mRNAs.
- Mn shared toxicological similarities with neurodegenerative diseases like Parkinson's, Alzheimer's, and Huntington's.
Conclusions:
- Mn exposure impairs eukaryotic cell biology, specifically by disrupting protein biosynthesis and ribosome function.
- These findings provide insights into the mechanisms of Mn-triggered cytotoxicity.
- Mn's toxicological pathways show parallels with those of major neurodegenerative diseases, highlighting potential shared etiological factors.
