Supplementary Material for: Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

Handle URI:
http://hdl.handle.net/10754/624133
Title:
Supplementary Material for: Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects
Authors:
Papsdorf, Katharina; Kaiser, Christoph; Drazic, Adrian; Grötzinger, Stefan W.; Haeßner, Carmen; Eisenreich, Wolfgang; Richter, Klaus
Abstract:
Abstract 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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Papsdorf, 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
Publisher:
Figshare
Issue Date:
2015
DOI:
10.6084/m9.figshare.c.3618170
Type:
Dataset
Is Supplement To:
Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects 2015, 16 (1) BMC Genomics; DOI:10.1186/s12864-015-1831-7; HANDLE:http://hdl.handle.net/10754/576984
Appears in Collections:
Datasets; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorPapsdorf, Katharinaen
dc.contributor.authorKaiser, Christophen
dc.contributor.authorDrazic, Adrianen
dc.contributor.authorGrötzinger, Stefan W.en
dc.contributor.authorHaeßner, Carmenen
dc.contributor.authorEisenreich, Wolfgangen
dc.contributor.authorRichter, Klausen
dc.date.accessioned2017-06-06T07:44:32Z-
dc.date.available2017-06-06T07:44:32Z-
dc.date.created2016-12-15en
dc.date.issued2015en
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.3618170en
dc.identifier.doi10.6084/m9.figshare.c.3618170en
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.en
dc.publisherFigshareen
dc.rightsCC BYen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectBiochemistryen
dc.subjectMicrobiologyen
dc.subjectCell Biologyen
dc.subjectGeneticsen
dc.subjectNeuroscienceen
dc.subjectCanceren
dc.subjectInfectious Diseasesen
dc.titleSupplementary Material for: Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defectsen
dc.typeDataseten
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
kaust.authorGrötzinger, Stefan W.en
dc.type.resourceCollectionen
dc.relation.isSupplementToPolyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects 2015, 16 (1) BMC Genomicsen
dc.relation.isSupplementToDOI:10.1186/s12864-015-1831-7en
dc.relation.isSupplementToHANDLE:http://hdl.handle.net/10754/576984en
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