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Updated: May 17, 2026

Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast
Published on: June 23, 2018
Protein aggregation caused by aminoglycoside action is prevented by a hydrogen peroxide scavenger
Jiqiang Ling1, Chris Cho, Li-Tao Guo
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Abstract:
Protein mistranslation causes growth arrest in bacteria, mitochondrial dysfunction in yeast, and neurodegeneration in mammals. It remains poorly understood how mistranslated proteins cause such cellular defects. Here we demonstrate that streptomycin, a bactericidal aminoglycoside that increases ribosomal mistranslation, induces transient protein aggregation in wild-type Escherichia coli. We further determined the aggregated proteome using label-free quantitative mass spectrometry. To identify genes that reduce cellular mistranslation toxicity, we selected from an overexpression library protein products that increased resistance against streptomycin and kanamycin. The selected proteins were significantly enriched in members of the oxidation-reduction pathway. Overexpressing one of these proteins, alkyl hydroperoxide reductase subunit F (a protein defending bacteria against hydrogen peroxide), but not its inactive mutant suppressed aggregated protein formation upon streptomycin treatment and increased aminoglycoside resistance. This work provides in-depth analyses of an aggregated proteome caused by streptomycin and suggests that cellular defense against hydrogen peroxide lowers the toxicity of mistranslation.
Insights
Streptomycin causes protein aggregation by increasing mistranslation in E. coli. Enhancing cellular defense against hydrogen peroxide reduces this toxicity, offering a new therapeutic strategy for mistranslation-related diseases.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Protein mistranslation is linked to cellular dysfunction, including bacterial growth arrest, yeast mitochondrial issues, and mammalian neurodegeneration.
- The precise mechanisms by which mistranslated proteins induce cellular defects are not fully understood.
Purpose of the Study:
- To investigate the effects of streptomycin, an aminoglycoside antibiotic that promotes ribosomal mistranslation, on protein aggregation in Escherichia coli.
- To identify cellular components or pathways that mitigate the toxicity associated with protein mistranslation.
Main Methods:
- Induced protein aggregation using streptomycin in wild-type E. coli.
- Characterized the aggregated proteome via label-free quantitative mass spectrometry.
- Screened an overexpression library to identify genes conferring resistance to streptomycin and kanamycin.
Main Results:
- Streptomycin treatment induced transient protein aggregation in E. coli.
- Proteins involved in oxidation-reduction pathways were significantly enriched among those conferring resistance.
- Overexpression of alkyl hydroperoxide reductase subunit F (AhpF) suppressed protein aggregation and increased aminoglycoside resistance.
Conclusions:
- Cellular defense mechanisms against hydrogen peroxide can reduce the toxicity of protein mistranslation.
- Targeting oxidative stress pathways may offer a therapeutic approach for conditions associated with protein mistranslation.
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