Isolation and characterization of carnitine acetyltransferase from S. cerevisiae

Kispál, Gyula; Csekö, József; Alkonyi, István; Sándor, Attila

doi:10.1016/0005-2760(91)90097-2

Cited by 36 publications

(27 citation statements)

References 20 publications

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“…ACS1 is also upregulated together with the glyoxylate cycle genes ICL1 and MLS1 upon incubation of C. albicans with neutrophils (8). The ACS1 product, a cytosolic enzyme in yeasts (12,28), catalyzes the ATP-dependent activation of acetate to acetyl-CoA. The cytosolic acetyl-CoA is either shuttled into mitochondria, requiring the carnitine acetyltransferase YAT1 localized in the outer mitochondrial membrane (26), or serves as a building block for lipid synthesis (7).…”

Section: Discussionmentioning

confidence: 99%

Peroxisomal Fatty Acid β-Oxidation Is Not Essential for Virulence of Candida albicans

Piekarska¹,

Mol²,

Berg³

et al. 2006

Eukaryot Cell

140

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Phagocytic cells form the first line of defense against infections by the human fungal pathogen Candida albicans. Recent in vitro gene expression data suggest that upon phagocytosis by macrophages, C. albicans reprograms its metabolism to convert fatty acids into glucose by inducing the enzymes of the glyoxylate cycle and fatty acid ␤-oxidation pathway. Here, we asked whether fatty acid ␤-oxidation, a metabolic pathway localized to peroxisomes, is essential for fungal virulence by constructing two C. albicans double deletion strains: a pex5⌬/pex5⌬ mutant, which is disturbed in the import of most peroxisomal enzymes, and a fox2⌬/ fox2⌬ mutant, which lacks the second enzyme of the ␤-oxidation pathway. Both mutant strains had strongly reduced ␤-oxidation activity and, accordingly, were unable to grow on media with fatty acids as a sole carbon source. Surprisingly, only the fox2⌬/fox2⌬ mutant, and not the pex5⌬/pex5⌬ mutant, displayed strong growth defects on nonfermentable carbon sources other than fatty acids (e.g., acetate, ethanol, or lactate) and showed attenuated virulence in a mouse model for systemic candidiasis. The degree of virulence attenuation of the fox2⌬/fox2⌬ mutant was comparable to that of the icl1⌬/icl1⌬ mutant, which lacks a functional glyoxylate cycle and also fails to grow on nonfermentable carbon sources. Together, our data suggest that peroxisomal fatty acid ␤-oxidation is not essential for virulence of C. albicans, implying that the attenuated virulence of the fox2⌬/fox2⌬ mutant is largely due to a dysfunctional glyoxylate cycle.

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Section: Discussionmentioning

confidence: 99%

Peroxisomal Fatty Acid β-Oxidation Is Not Essential for Virulence of Candida albicans

Piekarska¹,

Mol²,

Berg³

et al. 2006

Eukaryot Cell

140

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“…In addition to the capacity of the PDH-bypass enzymes, their subcellular localization may also be important. If acetyl-CoA synthetase is a cytosolic enzyme in K. lactis (as has been reported for S. cerevisiae; Kispal et al, 1991) this would imply that dissimilation of pyruvate via the PDH bypass requires transport of acetyl-CoA into the mitochondria, probably via a carnitine-transferase system (Kohlhaw & TanWilson, 1977). Further research into the regulation and subcellular compartmentation of PDH-bypass enzymes in K .…”

Section: Activities Of Key Enzymes In Cell Extractsmentioning

confidence: 93%

Inactivation of the Kluyveromyces lactis KIPDA1 gene leads to loss of pyruvate dehydrogenase activity, impairs growth on glucose and triggers aerobic alcoholic fermentation

et al. 1998

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Bioverfa hr ungstechn i k,University o f Stuttgart, Allmandring 31, D70569 S t u t t g a rt, Germ a n y 2 Kluyver Institute of 3 lnstitut fur The KlPDA1 gene, encoding the E l a subunit of the mitochondria1 pyruvatedehydrogenase (PDH) complex was isolated from a Kluyweromyces lactis genomic library by screening with a 1.1 kb internal fragment of the Saccharomyces cerewisiae PDA 1 gene. The predicted amino acid sequence encoded by KlPDA1 showed 87% similarity and 79% identity to its S. cerewisiae counterpart. Disruption of KlPDAI resulted in complete absence of PDH activity in cell extracts. The maximum specific growth rate on glucose of null mutants was 3.5-fold lower than that of the wild-type, whereas growth on ethanol was unaffected. Wild-type K. lactis CBS 2359 exhibits a Crabtreenegative phenotype, i.e. no ethanol was produced in aerobic batch cultures grown on glucose. In contrast, substantial amounts of ethanol and acetaldehyde were produced in aerobic cultures of an isogenic Klpda1 null mutant. A wild-type specific growth rate was restored after introduction of an intact KlPDA7 gene but not, as previously found for S. cerewisiae pdal mutants, by cultivation in the presence of leucine. The occurrence of aerobic fermentation and slow growth of the KlpdaI null mutant indicate that, although present, the enzymes of the PDH bypass (pyruvate decarboxylase, acetaldehyde dehydrogenase and acetyl-CoA synthetase) could not efficiently replace the PDH complex during batch cultivation on glucose. Only a t relatively low growth rates (D = 010 h-') in aerobic, glucose-limited chemostat cultures, could the PDH bypass completely replace the PDH complex, thus allowing fully respiratory growth. This resulted in a lower biomass yield [g biomass (g glucose)-l] than in the wild-type due to a higher consumption of ATP in the PDH bypass compared to the formation of acetyl-CoA via the PDH complex.

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“…The codon bias index (CBI) is shown on the right of each gene (Sharp and Cowe, 1991). contains two non-mitochondrial isozymes, Acs1p and Acs2p (Kispal et al, 1991;De Jong-Gubbels et al, 1996). ACS2, the gene encoding cytosolic Acs2p , was induced on ethanol (Figure 3).…”

Section: Ethanol Consumptionmentioning

confidence: 99%

Transient mRNA responses in chemostat cultures as a method of defining putative regulatory elements: Application to genes involved in Saccharomyces cerevisiae acetyl-coenzyme A metabolism

Berg

Jong-Gubbels

Steensma

1998

Yeast

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Isolation and characterization of carnitine acetyltransferase from S. cerevisiae

Cited by 36 publications

References 20 publications

Peroxisomal Fatty Acid β-Oxidation Is Not Essential for Virulence of Candida albicans

Peroxisomal Fatty Acid β-Oxidation Is Not Essential for Virulence of Candida albicans

Inactivation of the Kluyveromyces lactis KIPDA1 gene leads to loss of pyruvate dehydrogenase activity, impairs growth on glucose and triggers aerobic alcoholic fermentation

Transient mRNA responses in chemostat cultures as a method of defining putative regulatory elements: Application to genes involved in Saccharomyces cerevisiae acetyl-coenzyme A metabolism

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