Cadmium Causes Misfolding and Aggregation of Cytosolic Proteins in Yeast
Journal article, 2017

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.

zinc

protein degradation

protein folding

Saccharomyces cerevisiae

metal toxicity

protein aggregation

cadmium

Author

Therese Jacobson

University of Gothenburg

S. Priya

Indian Institute of Toxicology Research

S. K. Sharma

Indian Institute of Toxicology Research

S. Andersson

University of Gothenburg

Stefan Jakobsson

University of Gothenburg

R. Tanghe

University of Gothenburg

A. Ashouri

University of Gothenburg

Sahlgrenska Academy

Sebastien Rauch

Chalmers, Civil and Environmental Engineering, Water Environment Technology

P. Goloubinoff

University of Lausanne

P. Christen

University of Zürich

Markus J. Tamás

University of Gothenburg

Molecular and Cellular Biology

0270-7306 (ISSN)

Vol. 37 17 UNSP e00490-16

Subject Categories

Biological Sciences

DOI

10.1128/mcb.00490-16

More information

Latest update

3/23/2018