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dc.contributor.authorPapsdorf, Katharina
dc.contributor.authorKaiser, Christoph
dc.contributor.authorDrazic, Adrian
dc.contributor.authorGrötzinger, Stefan W.
dc.contributor.authorHaeßner, Carmen
dc.contributor.authorEisenreich, Wolfgang
dc.contributor.authorRichter, Klaus
dc.date.accessioned2017-06-06T07:44:32Z
dc.date.available2017-06-06T07:44:32Z
dc.date.created2016-12-15
dc.date.issued2015
dc.identifier.citationPapsdorf, K., Kaiser, C., Drazic, A., Grötzinger, S., HaeßNer, C., Eisenreich, W., & Richter, K. (2015). Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects. Figshare. https://doi.org/10.6084/m9.figshare.c.3618170
dc.identifier.doi10.6084/m9.figshare.c.3618170
dc.identifier.urihttp://hdl.handle.net/10754/624133
dc.description.abstractAbstract Background Protein aggregation and its pathological effects are the major cause of several neurodegenerative diseases. In Huntingtonâ s disease an elongated stretch of polyglutamines within the protein Huntingtin leads to increased aggregation propensity. This induces cellular defects, culminating in neuronal loss, but the connection between aggregation and toxicity remains to be established. Results To uncover cellular pathways relevant for intoxication we used genome-wide analyses in a yeast model system and identify fourteen genes that, if deleted, result in higher polyglutamine toxicity. Several of these genes, like UGO1, ATP15 and NFU1 encode mitochondrial proteins, implying that a challenged mitochondrial system may become dysfunctional during polyglutamine intoxication. We further employed microarrays to decipher the transcriptional response upon polyglutamine intoxication, which exposes an upregulation of genes involved in sulfur and iron metabolism and mitochondrial Fe-S cluster formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth is impossible after intoxication with the polyglutamine protein. NMR-based metabolic analyses reveal that mitochondrial metabolism is reduced, leading to accumulation of metabolic intermediates in polyglutamine-intoxicated cells. Conclusion These data show that damages to the mitochondrial system occur in polyglutamine intoxicated yeast cells and suggest an intricate connection between polyglutamine-induced toxicity, mitochondrial functionality and iron homeostasis in this model system.
dc.publisherfigshare
dc.rightsCC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBiochemistry
dc.subjectMicrobiology
dc.subjectCell Biology
dc.subjectGenetics
dc.subjectNeuroscience
dc.subjectCancer
dc.subjectInfectious Diseases
dc.titleSupplementary Material for: Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects
dc.typeDataset
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
kaust.personGrötzinger, Stefan W.
dc.type.resourceCollection
dc.relation.issupplementtoDOI:10.1186/s12864-015-1831-7
display.relations<b> Is Supplement To:</b> <br/> <ul><li><i>[Article]</i> <br/> Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects 2015, 16 (1) BMC Genomics. DOI: <a href="https://doi.org/10.1186/s12864-015-1831-7">10.1186/s12864-015-1831-7</a> HANDLE: <a href="http://hdl.handle.net/10754/576984">10754/576984</a></li></ul>


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