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

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

Research output: Contribution to journalArticle

16 Scopus citations


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
Issue number1
StatePublished - Jun 1 2008



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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this