Hsp104 as a key modulator of prion-mediated oxidative stress in Saccharomyces cerevisiae

Maintenance of cellular redox homeostasis forms an important part of the cellular defence mechanism and continued cell viability. Despite extensive studies, the role of the chaperone Hsp104 in propagation of misfolded protein aggregates in the cell and generation of oxidative stress remains poorly understood. Expression of RNQ1-RFP in Saccharomyces cerevisiae cells led to the generation of the prion form of the protein and increased oxidative stress. In this work, we show that disruption of Hsp104 in an isogenic yeast strain led to solubilisation of RNQ1-RFP. This reduced the oxidative stress generated in the cell. The higher level of oxidative stress in the Hsp104-containing (parental) strain correlated with lower activity of almost all intracellular antioxidant enzymes assayed. Surprisingly, this did not correspond with the gene expression analysis data. To compensate for the decrease in protein translation induced by a high level of reactive oxygen species, transcriptional upregulation takes place. This explains the discrepancies observed at the transcription level and functional enzymatic product. Our results show that in a ΔHsp104 strain, due to lower oxidative stress, no such mismatch is observed, corresponding with higher cell viability. Thus, Hsp104 is indirectly responsible for enhancing the oxidative stress in a prion-rich environment.

Source: BJ Cell - June 7, 2013 Category: Biochemistry Authors: K Singh, A A Saleh, A K Bhadra, I Roy Tags: BJ Disease Source Type: research