A toxic imbalance of Hsp70s in Saccharomyces cerevisiae is caused by competition for cofactors

Kathryn M. Keefer, Heather L. True: 2017 Molecular Microbiology Volume 105, Issue 6, September, Pages 860-868 Read More


Molecular chaperones are responsible for managing protein folding from translation through degradation. These crucial machines ensure that protein homeostasis is optimally maintained for cell health. However, ‘too much of a good thing’ can be deadly, and the excess of chaperones can be toxic under certain cellular conditions. For example, overexpression of Ssa1, a yeast Hsp70, is toxic to cells in folding-challenged states such as [PSI+]. We discovered that overexpression of the nucleotide exchange factor Sse1 can partially alleviate this toxicity. We further argue that the basis of the toxicity is related to the availability of Hsp70 cofactors, such as Hsp40 J-proteins and nucleotide exchange factors. Ultimately, our work informs future studies about functional chaperone balance and cautions against therapeutic chaperone modifications without a thorough examination of cofactor relationships. © 2017 John Wiley & Sons Ltd

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Posted on October 23, 2017
Posted in: HPAN, Neurodegeneration, Publications Authors: