Yeast Proteostasis under Acute Stress
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Date
2017-05-16
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Johns Hopkins University
Abstract
Protein homeostasis (proteostasis) is crucial to maintain normal cell activity. Loss of proteostasis is related to cell dysfunction and many neurodegenerative diseases. Protein aggregation is a sign of proteostasis loss. In this study, Saccharomyces cerevisiae(budding yeast) is used to study cell proteostasis under acute stress. After heat shock, misfolded proteins in yeast cells form cytosolic aggregates. An affinity based purification method based on model stress protein firefly luciferace towards aggregates is used and the component of aggregates is analyzed using MudPIT. Validation of the proteomics data showed most of them are cytosolic proteins and enrichment in mitochondria compartment. Imaging cells expressing split GFP showed aggregates go to mitochondria after heat shock and degraded by mitochondria. Disruption of mitochondria protease slow down aggregates dissolution. Disease related protein like TDP43 and α-synuclein are also related to mitochondria.
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Keywords
yeast, proteostais