Carnitine supplementation has protective and detrimental effects in Saccharomyces cerevisiae that are genetically mediated

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dc.contributor.authorFranken, J.en_ZA
dc.contributor.authorBauer, Florianen_ZA
dc.date.accessioned2011-05-15T16:03:26Z
dc.date.available2011-05-15T16:03:26Z
dc.date.issued2010
dc.description.abstractl-Carnitine plays a well-documented role in eukaryotic energy homeostasis by acting as a shuttling molecule for activated acyl residues across intracellular membranes. This activity, supported by carnitine acyl-transferases and transporters, is referred to as the carnitine shuttle. However, several pleiotropic and often beneficial effects of carnitine in humans have been reported that appear to be unrelated to shuttling activity, but little conclusive evidence regarding molecular mechanisms exists. We have recently demonstrated a role of carnitine, independent of the carnitine shuttle, in yeast stress protection. Here, we show that carnitine specifically protects against oxidative stress caused by H2O2 and the superoxide-generating agent menadione. Surprisingly, carnitine has a detrimental effect on survival when combined with thiol-modifying agents. Central elements of the oxidative stress response, specifically the transcription factors Yap1p and Skn7p, are shown to be required for carnitine's protective effect, but several downstream effectors are dispensable. A DNA microarray-based analysis identifies Cyc3p, a cytochrome c heme lyase, as being important for carnitine's impact during oxidative stress. These findings establish a direct genetic link to a carnitine-related phenotype that is independent of the shuttle system and suggests that Saccharomyces cerevisiae should provide a useful model for further elucidation of carnitine's physiological roles. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd.
dc.description.versionArticle
dc.identifier.citationFEMS Yeast Research
dc.identifier.citation10
dc.identifier.citation3
dc.identifier.issn15671356
dc.identifier.other10.1111/j.1567-1364.2010.00610.x
dc.identifier.urihttp://hdl.handle.net/10019.1/12617
dc.subjectcarnitine
dc.subjectcytochrome 3 heme lyase
dc.subjectcytochrome c
dc.subjectdiamide
dc.subjecthydrogen peroxide
dc.subjectmenadione
dc.subjectreactive oxygen metabolite
dc.subjecttranscription factor
dc.subjecttranscription factor Skn7p
dc.subjecttranscription factor Yap1
dc.subjectunclassified drug
dc.subjectarticle
dc.subjectcell damage
dc.subjectcell function
dc.subjectcell protection
dc.subjectconcentration (parameters)
dc.subjectcontrolled study
dc.subjectculture medium
dc.subjectDNA microarray
dc.subjectenrichment culture
dc.subjectgene expression
dc.subjectgenetic analysis
dc.subjectgenetic linkage
dc.subjectliquid culture
dc.subjectmicroarray analysis
dc.subjectnonhuman
dc.subjectoxidative stress
dc.subjectphenotype
dc.subjectprotein function
dc.subjectredox stress
dc.subjectSaccharomyces cerevisiae
dc.subjectsupplementation
dc.subjectAntioxidants
dc.subjectCarnitine
dc.subjectDNA-Binding Proteins
dc.subjectHydrogen Peroxide
dc.subjectLyases
dc.subjectMicrobial Viability
dc.subjectOxidants
dc.subjectOxidative Stress
dc.subjectSaccharomyces cerevisiae
dc.subjectSaccharomyces cerevisiae Proteins
dc.subjectStress, Physiological
dc.subjectTranscription Factors
dc.subjectVitamin B Complex
dc.subjectVitamin K 3
dc.subjectEukaryota
dc.subjectSaccharomyces cerevisiae
dc.titleCarnitine supplementation has protective and detrimental effects in Saccharomyces cerevisiae that are genetically mediated
dc.typeArticle
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