Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity
Artikel i vetenskaplig tidskrift, 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.

Translation

Protein misfolding

Protein aggregation

Arsenic

Proteostasis

Protein quality control

Yeast

Transcription

Författare

S. Andersson

Göteborgs universitet

Antonia Romero

Göteborgs universitet

Joana Isabel Rodrigues

Göteborgs universitet

Sansan Hua

Göteborgs universitet

Xinxin Hao

Göteborgs universitet

Therese Jacobson

Göteborgs universitet

Vivien Karl

Göteborgs universitet

Nathalie Becker

Göteborgs universitet

A. Ashouri

Göteborgs universitet

Sebastien Rauch

Chalmers, Arkitektur och samhällsbyggnadsteknik, Vatten Miljö Teknik

Thomas Nyström

Göteborgs universitet

Beidong Liu

Göteborgs universitet

Markus J. Tamás

Göteborgs universitet

Journal of Cell Science

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

Vol. 134 11

Ämneskategorier

Cellbiologi

Biokemi och molekylärbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1242/jcs.258338

PubMed

34085697

Mer information

Senast uppdaterat

2021-06-29