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Citation
Tags
HERO ID
1339148
Reference Type
Journal Article
Title
Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast
Author(s)
Jacobson, T; Navarrete, C; Sharma, SK; Sideri, TC; Ibstedt, S; Priya, S; Grant, CM; Christen, P; Goloubinoff, P; Tamás, MJ
Year
2012
Is Peer Reviewed?
Yes
Journal
Journal of Cell Science
ISSN:
0021-9533
EISSN:
1477-9137
Volume
125
Issue
21
Page Numbers
5073-5083
Language
English
PMID
22946053
DOI
10.1242/jcs.107029
Web of Science Id
WOS:000312984300015
Abstract
Several metals and metalloids profoundly affect biological systems, but their impact on the proteome and mechanisms of toxicity are not fully understood. Here, we demonstrate that arsenite causes protein aggregation in Saccharomyces cerevisiae. Various molecular chaperones were found to be associated with arsenite-induced aggregates indicating that this metalloid promotes protein misfolding. Using in vivo and in vitro assays, we show that proteins in the process of synthesis/folding are particularly sensitive to arsenite-induced aggregation, that arsenite interferes with protein folding by acting on unfolded polypeptides, and that arsenite directly inhibits chaperone activity. Thus, folding inhibition contributes to arsenite toxicity in two ways: by aggregate formation and by chaperone inhibition. Importantly, arsenite-induced protein aggregates can act as seeds committing other, labile proteins to misfold and aggregate. Our findings describe a novel mechanism of toxicity that may explain the suggested role of this metalloid in the etiology and pathogenesis of protein folding disorders associated with arsenic poisoning.
Keywords
Arsenic toxicity; Protein aggregation; Protein degradation; Protein folding; Yeast
Tags
IRIS
•
Arsenic (Inorganic)
1. Literature
PubMed
Lit search updates through Oct 2015
3. Hazard ID Screening
Other potentially supporting studies
4. Adverse Outcome Pathways/Networks Screening
Excluded/Not relevant
Title/Abstract screening
•
Arsenic MOA
1. MOA Literature Screening
Health Effect Screening
3. Excluded
Other not relevant
Dragon Screened
•
Inorganic Arsenic (7440-38-2) [Final 2025]
1. Initial Lit Search
PubMed
WOS
Considered New
2. Lit Search Updates through Oct 2015
WOS
Considered
4. Considered through Oct 2015
6. Cluster Filter through Oct 2015
7. Other Studies through Oct 2015
MOA
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