Genome-wide responses to mitochondrial dysfunction
Open accessAbstract
Mitochondrial dysfunction can lead to diverse cellular and organismal responses. We used DNA microarrays to characterize the transcriptional responses to different mitochondrial perturbations in Saccharomyces cerevisiae. We examined respiratory-deficient petite cells and respiratory-competent wild-type cells treated with the inhibitors of oxidative phosphorylation antimycin, carbonyl cyanide m-chlorophenylhydrazone, or oligomycin. We show that respiratory deficiency, but not inhibition of mitochondrial ATP synthesis per se, induces a suite of genes associated with both peroxisomal activities and metabolite-restoration (anaplerotic) pathways that would mitigate the loss of a complete tricarboxylic acid cycle. The array data suggested, and direct microscopic observation of cells expressing a derivative of green fluorescent protein with a peroxisomal matrix-targeting signal confirmed, that respiratory deficiency dramatically induces peroxisome biogenesis. Transcript profiling of cells harboring null alleles of RTG1, RTG2, or RTG3, genes known to control signaling from mitochondria to the nucleus, suggests that there are multiple pathways of cross-talk between these organelles in yeast.
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This aspect of the response shows some similarities between C. albicans and S. cerevisiae, as DIC1 and PEX11 are upregulated in respiratory-deficient ρ0 strains in S. cerevisiae, albeit by a different mechanism that does not involve the Rtg1/Rtg3 transcription factors.
“This aspect of the response shows some similarities between C. albicans and S. cerevisiae, as DIC1 and PEX11 are upregulated in the respiratory-deficient ρ0 strains in the latter, albeit by a different mechanism that does not involve the Rtg1/Rtg3 transcription factors (Epstein et al. 2001).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Epstein et al. 2001
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Experimental — accuracy not yet measuredOnly two C. albicans Rtg targets, DIC1 and PEX11, were found to be upregulated in respiratory-deficient strains of S. cerevisiae, albeit in a manner that does not depend on the Rtg transcription factors.
“Yet, only two of them—DIC1 and PEX11 were found to be upregulated in respiratory-deficient strains of S. cerevisiae, albeit in a manner that does not depend on the Rtg transcription factors (Epstein et al. 2001; Guaragnella et al. 2018).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Epstein et al. 2001
The Supplementary Material reports that DIC1 and PEX11 are upregulated in respiratory-deficient S. cerevisiae (ρ° cells), by 5.0- and 2.4-fold, respectively. The RTG Genes passage describes some induced genes as nearly RTG-independent, but does not establish that for DIC1 or PEX11 specifically. This paper also does not identify them as C. albicans Rtg targets or establish the 'only two' comparison. (LLM, conf=0.86)
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- Authors
- Epstein, C. B., Waddle, J. A., Hale, W., Davé, V., Thornton, J., Macatee, T. L., Garner, H. R., & Butow, R. A.
- Affiliations
- Department of Molecular Biology, and
- The University of Texas Southwestern Medical Center (US)
- Venue
- Molecular Biology of the Cell
- Published
- 2001-02
- Volume
- 12
- Issue
- 2
- Pages
- 297-308
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC30944
- OpenAlex
- W2114721511
- Cited by
- 389
- References
- 41
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 4 · 2022: 6 · 2021: 11 · 2020: 8 · 2019: 12 · 2018: 12 · 2017: 18 · 2016: 16 · 2015: 15 · 2014: 17 · 2013: 19 · 2012: 15
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca077811-03)
- National Institute on Aging (AG05781, F32AG005781)
- National Cancer Institute (CA77811)
- National Institute of General Medical Sciences (R37GM022525, GM22525)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial dysfunction, respiratory deficiency, Saccharomyces cerevisiae, transcriptional response, peroxisome biogenesis, peroxisomal metabolism, anaplerotic metabolism, TCA cycle, antimycin, CCCP, oligomycin, oxidative phosphorylation inhibition
- MeSH terms
- Antimycin A, Citric Acid Cycle, DNA-Binding Proteins, Enzyme Inhibitors, Fungal Proteins, Mitochondria, Oligomycins, Phosphorylation, Propionates, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Fungal, Genome, Fungal, Oligonucleotide Array Sequence Analysis, Peroxisomes, Gene Silencing, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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