title: Hsp104 as a key modulator of prion-mediated oxidative stress in Saccharomyces cerevisiae.
abstract: Maintenance of cellular redox homoeostasis forms an important part of the cellular defence mechanism and continued cell viability. Despite extensive studies, the role of the chaperone Hsp104 (heat-shock protein of 102 kDa) 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 the present study, we show that disruption of Hsp104 in an isogenic yeast strain led to solubilization 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 of the 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 up-regulation takes place. This explains the discrepancy observed between 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.
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
authors.forename: Kuljit
authors.initials: K
authors.lastname: Singh
authors.forename: Aliabbas A
authors.initials: AA
authors.lastname: Saleh
authors.forename: Ankan K
authors.initials: AK
authors.lastname: Bhadra
authors.forename: Ipsita
authors.initials: I
authors.lastname: Roy
mesh_terms: D015536:Down-Regulation; D015966:Gene Expression Regulation, Fungal; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050296:Microbial Viability; D009154:Mutation; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018621:PrPC Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011489:Protein Denaturation; D012331:RNA, Fungal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012995:Solubility; D015854:Up-Regulation; D000097573:Red Fluorescent Protein
chemical_list: D006360:Heat-Shock Proteins; D008164:Luminescent Proteins; D010088:Oxidoreductases; D018621:PrPC Proteins; D011328:Prions; D012331:RNA, Fungal; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097573:Red Fluorescent Protein; C404807:RNQ1 protein, S cerevisiae; C070972:HsP104 protein, S cerevisiae