Suppression of metabolic defects of yeast isocitrate dehydrogenase and aconitase mutants by loss of citrate synthase

An Ping Lin, Kevin W. Hakala, Susan E Weintraub, Lee McAlister-Henn

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Yeast mutants lacking mitochondrial NAD+-specific isocitrate dehydrogenase (idhΔ) or aconitase (aco1Δ) were found to share several growth phenotypes as well as patterns of specific protein expression that differed from the parental strain. These shared properties of idhΔ and aco1Δ strains were eliminated or moderated by co-disruption of the CIT1 gene encoding mitochondrial citrate synthase. Gas chromatography/mass spectrometry analyses indicated a particularly dramatic increase in cellular citrate levels in idhΔ and aco1Δ strains, whereas citrate levels were substantially lower in idhΔcit1Δ and aco1Δcit1Δ strains. Exogenous addition of citrate to parental strain cultures partially recapitulated effects of high endogenous levels of citrate in idhΔ and aco1Δ strains. Finally, effects of elevated cellular citrate in idhΔ and aco1Δ mutant strains were partially alleviated by addition of iron or by an increase in pH of the growth medium, suggesting that detrimental effects of citrate are due to elevated levels of the ionized form of this metabolite.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume474
Issue number1
DOIs
StatePublished - Jun 1 2008

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Aconitate Hydratase
Isocitrate Dehydrogenase
Citrate (si)-Synthase
Citric Acid
Yeast
Yeasts
Defects
Gene encoding
Mitochondrial Genes
Growth
Metabolites
Gas chromatography
NAD
Gas Chromatography-Mass Spectrometry
Mass spectrometry
Iron
Phenotype

Keywords

  • Aconitase
  • Citrate
  • Citrate synthase
  • Isocitrate dehydrogenase
  • Tricarboxylic acid cycle

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Suppression of metabolic defects of yeast isocitrate dehydrogenase and aconitase mutants by loss of citrate synthase. / Lin, An Ping; Hakala, Kevin W.; Weintraub, Susan E; McAlister-Henn, Lee.

In: Archives of Biochemistry and Biophysics, Vol. 474, No. 1, 01.06.2008, p. 205-212.

Research output: Contribution to journalArticle

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