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Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast
Published on: June 23, 2018
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A reversible liquid drop aggregation controls glucose response in yeast
Kobi Simpson-Lavy1, Martin Kupiec2
1School of Molecular Cell Biology & Biotechnology, Tel Aviv University, 69978, Ramat Aviv, Israel.
Current Genetics
|January 12, 2018
Summary
Yeast cells regulate metabolism by forming reversible Std1 protein aggregates in response to glucose levels. This process, controlled by Vhs1 kinase, sequesters SNF1 activators, impacting cellular respiration and fermentation pathways.
Area of Science:
- Cellular Biology
- Metabolic Regulation
- Biochemistry
Background:
- Saccharomyces cerevisiae utilizes glucose as its primary carbon source.
- Glucose depletion triggers SNF1 (yeast AMP-activated protein kinase-AMPK) activation, shifting cells from fermentation to respiration.
- Understanding SNF1 regulation is crucial for controlling cellular metabolic state.
Purpose of the Study:
- To elucidate the mechanism of SNF1 activity regulation by Std1 and Sip5.
- To characterize the role of the novel protein kinase Vhs1 in this regulatory pathway.
- To investigate the nature and physiological significance of Std1 sequestration.
Main Methods:
- Biochemical assays to study protein phosphorylation and interactions.
- Microscopy techniques to visualize protein localization and aggregation.
- Genetic manipulation of yeast strains to analyze gene function.
Main Results:
- Vhs1 phosphorylates Sip5 upon glucose availability, disrupting the Std1-Sip5 interaction.
- Std1 is sequestered into nucleus-vacuole junction puncta, which are liquid-like aggregates, not amyloids.
- This aggregation is reversible and requires protein chaperones, similar to pathological proteinopathies.
Conclusions:
- Vhs1-mediated phosphorylation of Sip5 controls Std1 localization and SNF1 activity.
- The study reveals a regulated, non-pathological role for protein aggregation in controlling major cellular metabolic pathways.
- This mechanism provides a novel insight into the dynamic regulation of cellular metabolism in yeast.
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