The nuclear transcription factor Rtg1p functions as a cytosolic, post-transcriptional regulator in the methylotrophic yeast Pichia pastoris
Open accessAbstract
Rtg1p and Rtg3p are two basic helix–loop–helix, retrograde transcription factors in the budding yeast Saccharomyces cerevisiae . Both factors heterodimerize to activate the transcription of nuclear genes in response to mitochondrial dysfunction and glutamate auxotrophy, but are not well characterized in other yeasts. Here, we demonstrate that the Rtg1p/Rtg3p-mediated retrograde signaling pathway is absent in the methylotrophic yeast Pichia pastoris . We observed that P. pastoris Rtg1p (PpRtg1p) heterodimerizes with S. cerevisiae Rtg3p and functions as a nuclear, retrograde transcription factor in S. cerevisiae , but not in P. pastoris. We noted that P. pastoris Rtg3p lacks a functional leucine zipper and interacts with neither S. cerevisiae Rtg1p (ScRtg1p) nor PpRtg1p. In the absence of an interaction with Rtg3p, PpRtg1p has apparently acquired a novel function as a cytosolic regulator of multiple P. pastoris metabolic pathways, including biosynthesis of glutamate dehydrogenase 2 and phosphoenolpyruvate carboxykinase required for the utilization of glutamate as the sole carbon source. PpRtg1p also had an essential role in methanol metabolism and regulated alcohol oxidase synthesis and was required for the metabolism of ethanol, acetate, and oleic acid, but not of glucose and glycerol. Although PpRtg1p could functionally complement ScRtg1p, ScRtg1p could not complement PpRtg1p, indicating that ScRtg1p is not a functional PpRtg1p homolog. Thus, PpRtg1p functions as a nuclear, retrograde transcription factor in S. cerevisiae and as a cytosolic, post-transcriptional regulator in P. pastoris . We conclude that PpRtg1p is a key component of a signaling pathway that regulates multiple metabolic processes in P. pastoris .
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The existence of the retrograde signaling pathway involving the Rtg transcription factors in Komagataella phaffii (Pichia pastoris) was challenged following the observation that the ortholog of Rtg3 in this species lacks conservation of key residues in the putative dimerization (Zip) domain and does not dimerize with Rtg1.
“The existence of the retrograde signaling pathway involving the Rtg transcription factors in Komagataella phaffii (Pichia pastoris) was challenged following the observation that the ortholog of Rtg3 in this species lacks conservation of key residues in the putative dimerization (Zip) domain and does not dimerize with Rtg1”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Dey et al. 2018
Despite the K. phaffii Rtg3 protein being shown incapable of forming heterodimers with the Rtg1 ortholog in vitro, based on sequence conservation it should nevertheless be considered an Rtg3 ortholog despite potential changes in function.
“In particular, even though the protein from K. phaffi was shown to be incapable of forming heterodimers with the Rtg1 ortholog in vitro (Dey et al. 2018), based on the sequence conservation it should nevertheless be considered as an Rtg3 ortholog despite potential changes in function.”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Dey et al. 2018
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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
- Authors
- Dey, T., Krishna Rao, K., Khatun, J., & Rangarajan, P. N.
- Affiliations
- Indian Institute of Science Bangalore (IN)
- Corresponding author
- Rangarajan, Pundi N.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 293
- Issue
- 43
- Pages
- 16647-16660
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC6204902
- OpenAlex
- W2890099438
- Cited by
- 16
- References
- 30
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- NOT FOUND REPOSITORY (Indian Institute of Science Bangalore) (acceptedVersion)
- Funders
- DST | Science and Engineering Research Board (EMR/2015/000567, SB/S2/JCB-025/2015)
- Department of Biotechnology, Ministry of Science and Technology (DBT-IISc partnership program)
- Department of Science and Technology, Ministry of Science and Technology (Fund for Improvement of S&T Infrastructure in Higher Educational Institutions)
- University Grants Commission (Centre for Advanced studies)
- 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
- retrograde signaling, Pichia pastoris, Saccharomyces cerevisiae, bHLH transcription factors, heterodimerization, leucine zipper, post-transcriptional regulation, phosphoenolpyruvate carboxykinase, methanol metabolism, alcohol oxidase, alcohol metabolism, acetate metabolism, functional complementation
- MeSH terms
- Amino Acid Sequence, Cell Nucleus, Cytosol, Fungal Proteins, Mitochondria, Pichia, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Signal Transduction, Gene Expression Regulation, Fungal, Sequence Homology, Saccharomyces cerevisiae Proteins, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Protein Interaction Domains and Motifs
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