Cadmium causes misfolding and aggregation of cytosolic proteins in yeast

Therese Jacobson, Smriti Priya, Sandeep K. Sharma, Stefanie Andersson, Sofia Jakobsson, Robbe Tanghe, Arghavan Ashouri, Sebastien Rauch, Pierre Goloubinoff, Philipp Christen, Markus J. Tamás*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Cadmium is a highly poisonous metal and is classified as a human carcinogen. While its toxicity is undisputed, the underlying in vivo molecular mechanisms are not fully understood. Here, we demonstrate that cadmium induces aggregation of cytosolic proteins in living Saccharomyces cerevisiae cells. Cadmium primarily targets proteins in the process of synthesis or folding, probably by interacting with exposed thiol groups in not-yet-folded proteins. On the basis of in vitro and in vivo data, we show that cadmium-aggregated proteins form seeds that increase the misfolding of other proteins. Cells that cannot efficiently protect the proteome from cadmium-induced aggregation or clear the cytosol of protein aggregates are sensitized to cadmium. Thus, protein aggregation may contribute to cadmium toxicity. This is the first report on how cadmium causes misfolding and aggregation of cytosolic proteins in vivo. The proposed mechanism might explain not only the molecular basis of the toxic effects of cadmium but also the suggested role of this poisonous metal in the pathogenesis of certain protein-folding disorders.

Original languageEnglish
Article numbere00490-16
JournalMolecular and Cellular Biology
Volume37
Issue number17
DOIs
StatePublished - 1 Sep 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 American Society for Microbiology. All Rights Reserved.

Keywords

  • Cadmium
  • Metal toxicity
  • Protein aggregation
  • Protein degradation
  • Protein folding
  • Saccharomyces cerevisiae
  • Zinc

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