Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity
Journal article, 2021

The toxic metalloid arsenic causes widespread misfolding and aggregation of cellular proteins. How these protein aggregates are formed in vivo, the mechanisms by which they affect cells and how cells prevent their accumulation is not fully understood. To find components involved in these processes, we performed a genome-wide imaging screen and identified Saccharomyces cerevisiae deletion mutants with either enhanced or reduced protein aggregation levels during arsenite exposure. We show that many of the identified factors are crucial to safeguard protein homeostasis (proteostasis) and to protect cells against arsenite toxicity. The hits were enriched for various functions including protein biosynthesis and transcription, and dedicated follow-up experiments highlight the importance of accurate transcriptional and translational control for mitigating protein aggregation and toxicity during arsenite stress. Some of the hits are associated with pathological conditions, suggesting that arsenite-induced protein aggregation may affect disease processes. The broad network of cellular systems that impinge on proteostasis during arsenic stress identified in this current study provides a valuable resource and a framework for further elucidation of the mechanistic details of metalloid toxicity and pathogenesis. This article has an associated First Person interview with the first authors of the paper.


Protein misfolding

Protein aggregation



Protein quality control




S. Andersson

University of Gothenburg

Antonia Romero

University of Gothenburg

Joana Isabel Rodrigues

University of Gothenburg

Sansan Hua

University of Gothenburg

Xinxin Hao

University of Gothenburg

Therese Jacobson

University of Gothenburg

Vivien Karl

University of Gothenburg

Nathalie Becker

University of Gothenburg

A. Ashouri

University of Gothenburg

Sebastien Rauch

Chalmers, Architecture and Civil Engineering, Water Environment Technology

Thomas Nyström

University of Gothenburg

Beidong Liu

University of Gothenburg

Markus J. Tamás

University of Gothenburg

Journal of Cell Science

0021-9533 (ISSN) 1477-9137 (eISSN)

Vol. 134 11 jcs258338

Subject Categories

Cell Biology

Biochemistry and Molecular Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)





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4/5/2022 7