US EPA

1339148 

Journal Article 

Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast 

Jacobson, T; Navarrete, C; Sharma, SK; Sideri, TC; Ibstedt, S; Priya, S; Grant, CM; Christen, P; Goloubinoff, P; Tamás, MJ 

2012 

Yes 

Journal of Cell Science
ISSN: 0021-9533
EISSN: 1477-9137 

125 

21 

5073-5083 

English 

22946053 

10.1242/jcs.107029 

WOS:000312984300015 

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. 

Arsenic toxicity; Protein aggregation; Protein degradation; Protein folding; Yeast