Summary of Study ST002478
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001601. The data can be accessed directly via it's Project DOI: 10.21228/M8RH99 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002478 |
| Study Title | The effect of prions on cellular metabolism: The metabolic impact of the [RNQ+] prion and the native role of Rnq1p |
| Study Summary | Within the field of amyloid and prion disease there is a need for a more comprehensive understanding of the fundamentals of disease biology. In order to facilitate the progression treatment and underpin comprehension of toxicity, fundamental understanding of the disruption to normal cellular biochemistry and trafficking is needed. Here, by removing the complex biochemistry of the brain, we have utilised known prion forming strains of Saccharomyces cerevisiae carrying different conformational variants of the Rnq1p to obtain Liquid Chromatography-Mass Spectrometry (LC-MS) metabolic profiles and identify key perturbations of prion presence. These studies reveal that prion containing [RNQ+] cells display a significant reduction in amino acid biosynthesis and distinct perturbations in sphingolipid metabolism, with significant downregulation in metabolites within these pathways. Moreover, that native Rnq1p downregulates ubiquinone biosynthesis pathways within cells, suggesting that Rnq1p may play a lipid/mevalonate-based cytoprotective role as a regulator of ubiquinone production. These findings contribute to the understanding of how prion proteins interact in vivo in both their prion and non-prion confirmations and indicate potential targets for the mitigation of these effects. . We demonstrate specific sphingolipid centred metabolic disruptions due to prion presence and give insight into a potential cytoprotective role of the native Rnq1 protein. This provides evidence of metabolic similarities between yeast and mammalian cells as a consequence of prion presence and establishes the application of metabolomics as a tool to investigate prion/amyloid-based phenomena. |
| Institute | Canterbury Christ Church University |
| Last Name | Howell-Bray |
| First Name | Tyler |
| Address | 46 Canterbury Road, Kent |
| t.l.howellbray@gmail.com | |
| Phone | 07841631495 |
| Submit Date | 2022-10-12 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-02-26 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO002561 |
| Collection Summary: | Strain and cultivation conditions The S. cerevisiae strain used in this study were derivatives of 74-D694 (MATa ade1-14(UGA) trp1-289(UAG) ura3-52 his3-∆200 leu2-3, 112) (Chernoff et al. 1993). Yeast harbouring [RNQ+] and knockout strain Δrnq were kind gifts from the Kent Fungal Group. Yeast were grown at 30°C with shaking at 180 rpm in synthetic complete (SC) media (2 % (w/v) glucose, 0.17 % Yeast Nitrogen Base (without amino acids, without ammonium sulphate), 0.5% ammonium sulphate, the appropriate concentration of yeast synthetic complete supplement mixture or synthetic complete drop-out media supplement). Transient growth on SC media containing 3mM guanidine hydrochloride (GdnHCl) was used as a curing agent in the media of S. cerevisiae cells that required a [prion-] status. Mild oxidative stresses were achieved by the addition of H2O2 (final concentration 0.2 mM) to the appropriate culture mediums. Cultures were grown using the filter culture method (as described by rabinowiz 2008) |
| Sample Type: | Yeast cells |
| Storage Conditions: | -80℃ |
