The <i>CIT3</i> gene of <i>Saccharomyces cerevisiae</i> encodes a second mitochondrial isoform of citrate synthase

Jia, Yankai; Bécam, A.‐M.; Herbert, Christopher J.

doi:10.1046/j.1365-2958.1997.3011669.x

Cited by 45 publications

(38 citation statements)

References 24 publications

(38 reference statements)

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“…Pyruvic acid and three neighboring TCA cycle intermediates (oxaloacetic acid, citric acid, and isocitric acid) significantly increased after 11 generations. Citrate synthase catalyzes the condensation of acetyl coenzyme A and oxaloacetate to form citrate and is the rate-limiting enzyme in the TCA cycle (26,27). Interestingly, the transcript levels of the CIT1, CIT2, and CIT3 genes, which encode citrate synthase, are increased in senescent cells according to DNA microarray analysis (Fig.…”

Section: Pathways That Are Transcriptionally Changed During the Earlymentioning

confidence: 99%

Changes in Transcription and Metabolism During the Early Stage of Replicative Cellular Senescence in Budding Yeast

Kamei

Tamada

Nakayama

et al. 2014

Journal of Biological Chemistry

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Background: Senescence is the biological process of age-related cellular and organismal deterioration in function. Results: The transcriptome and metabolome at early stages of replicative senescence of yeast cells were measured. Conclusion: The transcriptomic and metabolomic profiles drastically changed at about half of the average replicative lifespan. Significance: This is the first integrated information on transcriptome and metabolome of aging yeast cells.

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Section: Pathways That Are Transcriptionally Changed During the Earlymentioning

confidence: 99%

Changes in Transcription and Metabolism During the Early Stage of Replicative Cellular Senescence in Budding Yeast

Kamei

Tamada

Nakayama

et al. 2014

Journal of Biological Chemistry

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“…In S. cerevisiae, activation of propionate to propionyl-CoA can be catalyzed by the ACS1-encoded isoenzyme of acetyl-CoA synthetase (36), and propionyl-CoA is a substrate for the acetylcarnitine transferase shuttle (21). Likely candidate genes for the 2-methylcitrate synthase-encoding gene are CIT1, CIT2, and CIT3, which all encode active citrate synthase isoenzymes (15). In glucose-limited chemostat cultures fed with increasing concentrations of propionate as a cosubstrate, induction of 2-methylcitrate synthase activity was paralleled by an increase in citrate synthase activity (23).…”

Section: Discussionmentioning

confidence: 99%

TheSaccharomyces cerevisiae ICL2Gene Encodes a Mitochondrial 2-Methylisocitrate Lyase Involved in Propionyl-Coenzyme A Metabolism

et al. 2000

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The Saccharomyces cerevisiae ICL1 gene encodes isocitrate lyase, an essential enzyme for growth on ethanol and acetate. Previous studies have demonstrated that the highly homologous ICL2 gene (YPR006c) is transcribed during the growth of wild-type cells on ethanol. However, even when multiple copies are introduced, ICL2 cannot complement the growth defect of icl1 null mutants. It has therefore been suggested that ICL2 encodes a nonsense mRNA or nonfunctional protein. In the methylcitrate cycle of propionyl-coenzyme A metabolism, 2-methylisocitrate is converted to succinate and pyruvate, a reaction similar to that catalyzed by isocitrate lyase. To investigate whether ICL2 encodes a specific 2-methylisocitrate lyase, isocitrate lyase and 2-methylisocitrate lyase activities were assayed in cell extracts of wild-type S. cerevisiae and of isogenic icl1, icl2, and icl1 icl2 null mutants. Isocitrate lyase activity was absent in icl1 and icl1 icl2 null mutants, whereas in contrast, 2-methylisocitrate lyase activity was detected in the wild type and single icl mutants but not in the icl1 icl2 mutant. This demonstrated that ICL2 encodes a specific 2-methylisocitrate lyase and that the ICL1-encoded isocitrate lyase exhibits a low but significant activity with 2-methylisocitrate. Subcellular fractionation studies and experiments with an ICL2-green fluorescent protein fusion demonstrated that the ICL2-encoded 2-methylisocitrate lyase is located in the mitochondrial matrix. Similar to that of ICL1, transcription of ICL2 is subject to glucose catabolite repression. In glucose-limited cultures, growth with threonine as a nitrogen source resulted in a ca. threefold induction of ICL2 mRNA levels and of 2-methylisocitrate lyase activity in cell extracts relative to cultures grown with ammonia as the nitrogen source. This is consistent with an involvement of the 2-methylcitrate cycle in threonine catabolism.The complete sequencing of the Saccharomyces cerevisiae genome has yielded a large number of open reading frames with unknown function (11). Some of the newly discovered open reading frames exhibited a strong homology with known yeast genes and were demonstrated to encode hitherto-unknown isoenzymes. An example is the PYK2 gene, which encodes a pyruvate kinase isoenzyme but can restore growth of pyk1 null mutants on glucose only when overexpressed (3). In other cases, the biochemical function of the proteins (if any) encoded by the homologous open reading frames remains unknown.An intriguing case is presented by the ICL2 gene. This gene (YPR006c) exhibits a substantial sequence similarity with ICL1 (13), the unique S. cerevisiae structural gene encoding isocitrate lyase (38% identity at the amino acid level). Isocitrate lyase is a key enzyme of the glyoxylate cycle. As this pathway is essential for growth on acetate and ethanol, icl1 null mutants are unable to grow on ethanol or acetate (9, 28). ICL2 is transcribed in ethanol-grown cultures of wild-type S. cerevisiae, and experiments with ICL2-lacZ fusions indicated that its tra...

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“…Three distinct S. cerevisiae genes encoding CSs have been identified: CIT1 (Suissa et al, 1984) and CIT3 (Jia et al, 1997) code for the mitochondrial isoforms and CIT2 for the peroxisomal isoform. While the mitochondrial Cit1 (Suissa et al, 1984) is involved in the TCA cycle, its peroxisomal isoform Cit2 functions in the glyoxylate cycle (Lewin et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

TCA cycle‐independent acetate metabolism via the glyoxylate cycle in Saccharomyces cerevisiae

Lee

Jang

Kim

et al. 2010

Yeast

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In Saccharomyces cerevisiae, the accepted theory is that due to TCA cycle dysfunction, the cit1 mutant lacking the mitochondrial enzyme citrate synthase (Cit1) cannot grow on acetate, regardless of the presence of the peroxisomal isoenzyme (Cit2). In this study, we re-evaluated the roles of Cit1 and Cit2 in acetate utilization and examined the pathway of acetate metabolism by analysing mutants defective in TCA or glyoxylate cycle enzymes. Although cit1 cells showed significantly reduced growth on rich acetate medium (YPA), they exhibited growth similar to cit2 and the wild-type cells on minimal acetate medium (YNBA). Impaired acetate utilization by cit1 cit2 cells on YNBA was restored by ectopic expression of either Cit2 or its cytoplasmically localized variants. Deletion of any of the genes for the enzymes solely involved in the TCA cycle (IDH1, KGD1 and LSC1 ), except for SDH1, caused little defect in acetate utilization on YNBA but resulted in significant growth impairment on YPA. In contrast, cells lacking any of the genes involved in the glyoxylate cycle (ACO1, FUM1, MLS1, ICL1 and MDH2 ) did not grow on either YNBA or YPA. Deletion of SFC1 encoding the succinate-fumarate carrier also caused similar growth defects on YNBA. Our results suggest that in S. cerevisiae the glyoxylate cycle functions as a competent metabolic pathway for acetate utilization on YNBA, while both the TCA and glyoxylate cycles are essential for growth on YPA.

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The CIT3 gene of Saccharomyces cerevisiae encodes a second mitochondrial isoform of citrate synthase

Cited by 45 publications

References 24 publications

Changes in Transcription and Metabolism During the Early Stage of Replicative Cellular Senescence in Budding Yeast

Changes in Transcription and Metabolism During the Early Stage of Replicative Cellular Senescence in Budding Yeast

TheSaccharomyces cerevisiae ICL2Gene Encodes a Mitochondrial 2-Methylisocitrate Lyase Involved in Propionyl-Coenzyme A Metabolism

TCA cycle‐independent acetate metabolism via the glyoxylate cycle in Saccharomyces cerevisiae

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