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Cadmium Causes Misfolding and Aggregation of Cytosolic Proteins in Yeast

T. Jacobson ; S. Priya ; S. K. Sharma ; S. Andersson ; S. Jakobsson ; R. Tanghe ; A. Ashouri ; Sebastien Rauch (Institutionen för arkitektur och samhällsbyggnadsteknik, Vatten miljö teknik) ; P. Goloubinoff ; P. Christen ; M. J. Tamas
Molecular and Cellular Biology (0270-7306). Vol. 37 (2017), 17, p. UNSP e00490-16.
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: metal toxicity, protein aggregation, protein degradation, protein folding, Saccharomyces cerevisiae, cadmium, zinc



Denna post skapades 2017-09-20.
CPL Pubid: 252002

 

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Institutioner (Chalmers)

Institutionen för arkitektur och samhällsbyggnadsteknik, Vatten miljö teknik

Ämnesområden

Biologiska vetenskaper

Chalmers infrastruktur