RetroGREAT signaling: The lessons we learn from yeast
Abstract
The mitochondrial retrograde signaling (RTG) pathway of communication from mitochondria to the nucleus was first studied in yeast Saccharomyces cerevisiae. It rewires cellular metabolism according to the mitochondrial state by reprogramming nuclear gene expression in response to mitochondrial triggers. The main players involved in retrograde signaling are the Rtg1 and Rtg3 transcription factors, and a set of positive and negative regulators, including the Rtg2, Mks1, Lst8, and Bmh1/2 proteins. Retrograde regulation is integrated with other processes, including stress response, osmoregulation, and nutrient sensing through functional crosstalk with cellular pathways such as high osmolarity glycerol or target of rapamycin signaling. In this review, we summarize metabolic changes observed upon retrograde stimulation and analyze the progress made to uncover the mechanisms underlying the integration of regulatory circuits. Comparisons of the evolutionary adaptations of the retrograde pathway that have occurred in the different yeast groups can help to fully understand the process.
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The activation of AOX by the Rtg pathway suggests that its function in the retrograde response to mitochondrial dysfunction could be conserved in C. albicans despite the considerable evolutionary distance from S. cerevisiae and many changes in the components of the pathway, the mitochondrial genome and respiratory metabolism.
“The activation of AOX by the Rtg pathway suggests that its function in the retrograde response to mitochondrial dysfunction could be conserved in C. albicans despite the considerable evolutionary distance from S. cerevisiae and many changes in the components of the pathway”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Bui and Labedzka-Dmoch 2024
The main regulatory proteins Rtg2 and Mks1 do not have orthologs in C. albicans.
“The main regulatory proteins Rtg2 and Mks1 do not have orthologs in C. albicans”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Bui and Labedzka-Dmoch 2024
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“3,26 64 – 66 Notably, these species possess the AOX gene and mitochondrially encoded complex I of NADH: ubiquinon oxidoreductase, 59,65 – 68 which are present in many yeasts and fungi, but absent from S. cerevisiae and S. pombe .”
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Łabędzka-Dmoch, K., Bui, T. H. D., Piątkowski, J., Dilling, M., Jagiełło, P., Kabza, W., & Golik, P. (2026) · Molecular Biology and Evolution · doi:10.1093/molbev/msag005 · Cited by 1 · see citing works
Self-citation
- Authors
- Bui, T. H. D., & Labedzka‐Dmoch, K.
- Affiliations
- University of Warsaw (PL)
- Institute of Genetics and Biotechnology, Faculty of Biology University of Warsaw Warsaw Poland
- Venue
- IUBMB Life
- Publisher
- Wiley
- Published
- 2023-08-10
- Volume
- 76
- Issue
- 1
- Pages
- 26-37
- ISSN
- 1521-6543 (ISSN-L)
- 1521-6551
- OpenAlex
- W4385724859
- Cited by
- 14
- References
- 10
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 3 · 2023: 1
- FWCI
- 0.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- IUBMB Life (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial retrograde signaling, Saccharomyces cerevisiae, MKS1, LST8, mitochondrial-nuclear communication, metabolic reprogramming, nuclear gene expression regulation, osmoregulation, TOR signaling, stress response, nutrient sensing, adaptive evolution, yeast
- MeSH terms
- Cell Nucleus, Saccharomyces cerevisiae, Transcription Factors, Signal Transduction, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae Proteins
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