Arsenite treatment induces Hsp90 aggregates distinct from conventional stress granules in fission yeast
Authors:Naofumi Tomimotoa, Teruaki Takasakia and Reiko Sugiura
doi: 10.15698/mic2024.07.829
Volume 11, pp. 242 to 253, published 19/07/2024.
Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Higashiosaka, Osaka 577-8502, Japan
Keywords:
Hsp90, aggregates, stress granules, fission yeast, arsenite.
Corresponding Author(s):
Conflict of interest statement:
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Please cite this article as:
Naofumi Tomimoto, Teruaki Takasaki, Reiko Sugiura (2024). Arsenite treatment induces Hsp90 aggregates distinct from conventional stress granules in fission yeast. Microbial Cell 11: 242-253. doi: 10.15698/mic2024.07.829
© 2024 Tomimoto et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Various stress conditions, such as heat stress (HS) and oxidative stress, can cause biomolecular condensates represented by stress granules (SGs) via liquid-liquid phase separation. We have previously shown that Hsp90 forms aggregates in response to HS and that Hsp90 aggregates transiently co- localize with SGs as visualized by Pabp. Here, we showed that arsenite, one of the well-described SG-inducing stimuli, induces Hsp90 aggregates distinct from conventional SGs in fission yeast. Arsenite induced Hsp90 granules in a dose- dependent manner, and these granules were significantly diminished by the co- treatment with a ROS scavenger N-acetyl cysteine (NAC), indicating that ROS are required for the formation of Hsp90 granules upon arsenite stress. Notably, Hsp90 granules induced by arsenite do not overlap with conventional SGs as represented by eIF4G or Pabp, while HS-induced Hsp90 granules co-localize with SGs. Nrd1, an RNA-binding protein known as a HS-induced SG component, was recruited into Hsp90 aggregates but not to the conventional SGs upon arsenite stress. The non-phosphorylatable eIF2α mutants significantly delayed the Hsp90 granule formation upon arsenite treatment. Importantly, inhibition of Hsp90 by geldanamycin impaired the Hsp90 granule formation and reduced the arsenite tolerance. Collectively, arsenite stimulates two types of distinct aggregates, namely conventional SGs and a novel type of aggregates containing Hsp90 and Nrd1, wherein Hsp90 plays a role as a center for aggregation, and stress-specific compartmentalization of biomolecular condensates.