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

Therese Jacobson, Clara Navarrete, Sandeep K. Sharma, Theodora C. Sideri, Sebastian Ibstedt, Smriti Priya, Chris M. Grant, Philipp Christen, Pierre Goloubinoff, Markus J. Tamá*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)5073-5083
Number of pages11
JournalJournal of Cell Science
Issue number21
StatePublished - 2012
Externally publishedYes


FundersFunder number
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung140512


    • Arsenic toxicity
    • Protein aggregation
    • Protein degradation
    • Protein folding
    • Yeast


    Dive into the research topics of 'Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast'. Together they form a unique fingerprint.

    Cite this