Cited by 290Fungal and yeast genetics researchMitochondrial Function and PathologyBacterial Genetics and Biotechnology

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A Transcriptional Switch in the Expression of Yeast Tricarboxylic Acid Cycle Genes in Response to a Reduction or Loss of Respiratory Function

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Liu, Zhengchang, Butow, Ronald A.·1999·Molecular and Cellular Biology

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Abstract

The Hap2,3,4,5p transcription complex is required for expression of many mitochondrial proteins that function in electron transport and the tricarboxylic acid (TCA) cycle. We show that as the cells' respiratory function is reduced or eliminated, the expression of four TCA cycle genes, CIT1, ACO1, IDH1, and IDH2, switches from HAP control to control by three genes, RTG1, RTG2, and RTG3. The expression of four additional TCA cycle genes downstream of IDH1 and IDH2 is independent of the RTG genes. We have previously shown that the RTG genes control the retrograde pathway, defined as a change in the expression of a subset of nuclear genes, e.g., the glyoxylate cycle CIT2 gene, in response to changes in the functional state of mitochondria. We show that the cis-acting sequence controlling RTG-dependent expression of CIT1 includes an R box element, GTCAC, located 70 bp upstream of the Hap2,3,4,5p binding site in the CIT1 upstream activation sequence. The R box is a binding site for Rtg1p-Rtg3p, a heterodimeric, basic helix-loop-helix/leucine zipper transcription factor complex. We propose that in cells with compromised mitochondrial function, the RTG genes take control of the expression of genes leading to the synthesis of alpha-ketoglutarate to ensure that sufficient glutamate is available for biosynthetic processes and that increased flux of the glyoxylate cycle, via elevated CIT2 expression, provides a supply of metabolites entering the TCA cycle sufficient to support anabolic pathways. Glutamate is a potent repressor of RTG-dependent expression of genes encoding both mitochondrial and nonmitochondrial proteins, suggesting that it is a specific feedback regulator of the RTG system.

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Authors: Liu, Z., & Butow, R. A.
Affiliations: The University of Texas Southwestern Medical Center (US)
Corresponding author: Butow, Ronald A.
ORCID: Liu, Zhengchang
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 1999-10-01
Volume: 19
Issue: 10
Pages: 6720-6728
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.19.10.6720
PMC: PMC84662
OpenAlex: W2102284511
Cited by: 290
References: 50
Citations by year: 2026: 5 · 2025: 4 · 2024: 14 · 2023: 12 · 2022: 7 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 8 · 2017: 10 · 2016: 7 · 2015: 7 · 2014: 14 · 2013: 17 · 2012: 13
FWCI: 4.60
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Welch Foundation
National Institutes of Health
National Institute of General Medical Sciences (R37GM022525, GM22525)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords: transcriptional switch, retrograde signaling, mitochondrial dysfunction, respiratory deficiency, glyoxylate cycle, alpha-ketoglutarate, IDH1, IDH2, ACO1, Saccharomyces cerevisiae
MeSH terms: Aconitate Hydratase, Binding Sites, Citrate (si)-Synthase, Citric Acid Cycle, DNA-Binding Proteins, Fungal Proteins, Genes, Fungal, Genes, Switch, Isocitrate Dehydrogenase, Models, Genetic, Oxygen Consumption, Phenotype, Protein Binding, Saccharomyces cerevisiae, Transcription Factors, Gene Expression Regulation, Fungal, Gene Deletion, Genes, Reporter, Glutamic Acid, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors

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A Transcriptional Switch in the Expression of Yeast Tricarboxylic Acid Cycle Genes in Response to a Reduction or Loss of Respiratory Function

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