Hsp90 Maintains Proteostasis of the Galactose Utilization Pathway To Prevent Cell Lethality

Abstract

Hsp90 is a molecular chaperone that aids in the folding of its metastable client proteins. Past studies have shown that it can exert a strong impact on some cellular pathways by controlling key regulators. However, it is unknown whether several components of a single pathway are collectively regulated by Hsp90. Here, we observe that Hsp90 influences the protein abundance of multiple Gal proteins and the efficiency of galactose utilization even after the galactose utilization pathway (GAL pathway) is fully induced. The effect of Hsp90 on Gal proteins is not at the transcriptional level. Moreover, Gal1 is found to physically interact with Hsp90, and its stability is reduced in low-Hsp90 cells. When Hsp90 is compromised, several Gal proteins form protein aggregates that colocalize with the disaggregase Hsp104. These results suggest that Gal1 and other Gal proteins are probably the clients of Hsp90. An unbalanced GAL pathway has been known to cause fatal growth arrest due to accumulation of toxic galactose metabolic intermediates. It is likely that Hsp90 chaperones multiple Gal proteins to maintain proteostasis and prevent cell lethality especially in a fluctuating environment.

ACKNOWLEDGMENTS

We acknowledge the contribution of Y.-Y. Hsieh in constructing the TETp-HSC82 GAL1-GFP strain and her initial observation that led to this study. We thank W.-S. Lo, S. C. Schuyler, H.-C. Yen, M.-C. Yao, and members of the Leu lab for helpful discussions and comments on the project. We also thank John O'Brien for editing the manuscript and the Imaging and Genomics Cores of IMB for technical assistance.

This work was supported by Academia Sinica of Taiwan (grant 100-CDA-L04) and the Taiwan Ministry of Science and Technology (104-2321-B-001-058).

We declare that we have no conflicts of interest.

R.K.G. and J.-Y.L. conceived the study, designed analyses, and interpreted results. R.K.G. performed the experiments. R.K.G. and J.-Y.L. wrote the paper.

Additional information

Funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.