RTG1 and RTG2: two yeast genes required for a novel path of communication from mitochondria to the nucleus
Abstract
The expression of some nuclear genes is sensitive to the functional state of mitochondria, a process we term retrograde regulation. Here we show that retrograde regulation of the yeast CIT2 gene encoding peroxisomal citrate synthase depends on a new class of upstream activation site element (UASr) and two previously unidentified genes, RTG1 and RTG2. RTG1 encodes a protein of 177 amino acids with similarity to basic helix-loop-helix transcription factors that likely functions at the CIT2 UASr. RTG2 encodes a protein of 394 amino acids of unknown function. Cells containing null alleles of RTG1 and RTG2 are viable and respiratory competent. However, they are auxotrophic for glutamic or aspartic acid and cannot use acetate as a sole carbon source, suggesting that both the tricarboxylic acid and glyoxylate cycles are compromised. Thus, RTG1 and RTG2 are pivotal genes in controlling interorganelle communication between mitochondria, peroxisomes, and the nucleus.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The retrograde (Rtg) signaling pathway was first described in S. cerevisiae, where it coordinates nuclear and mitochondrial gene expression.
“The retrograde (Rtg) signaling pathway was first described in model yeast Saccharomyces cerevisiae, where it is responsible for the function of coordinating nuclear and mitochondrial gene expression”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Liao and Butow 1993
Cites
The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation
Davis, R. L., Cheng, P.-F., Lassar, A. B., & Weintraub, H. (1990) · Cell · doi:10.1016/0092-8674(90)90088-v · Cited by 765 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A mitochondrial specific stress response in mammalian cells
Zhao, Q., Wang, J., Levichkin, I. V., Stasinopoulos, S., Ryan, M. T., & Hoogenraad, N. J. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf445 · Cited by 1,026 · see citing works
Butow, R. A., & Avadhani, N. G. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00179-0 · Cited by 882 · see citing works
Self-citationGenome-wide responses to mitochondrial dysfunction
Epstein, C. B., Waddle, J. A., Hale, W., Davé, V., Thornton, J., Macatee, T. L., Garner, H. R., & Butow, R. A. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.2.297 · Cited by 389 · see citing works
Self-citationBiswas, G., Adebanjo, O. A., Freedman, B. D., Anandatheerthavarada, H. K., Vijayasarathy, C., Zaidi, M., Kotlikoff, M., & Avadhani, N. G. (1999) · The EMBO Journal · doi:10.1093/emboj/18.3.522 · Cited by 369 · see citing works
Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance
Tigano, M., Vargas, D. C., Tremblay-Belzile, S., Fu, Y., & Sfeir, A. (2021) · Nature · doi:10.1038/s41586-021-03269-w · Cited by 327 · see citing works
Interorganelle signaling is a determinant of longevity in Saccharomyces cerevisiae
Kirchman, P. A., Kim, S., Lai, C.-Y., & Jazwinski, S. M. (1999) · Genetics · doi:10.1093/genetics/152.1.179 · Cited by 328 · see citing works
Liu, Z., & Butow, R. A. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.10.6720 · Cited by 290 · see citing works
Self-citationRecent developments in yeast aging
Kaeberlein, M., Burtner, C. R., & Kennedy, B. K. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030084 · Cited by 239 · see citing works
Jia, Y., Rothermel, B., Thornton, J., & Butow, R. A. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1110 · Cited by 219 · see citing works
Self-citationJackson, C. A., Castro, D. M., Saldi, G.-A., Bonneau, R., & Gresham, D. (2020) · eLife · doi:10.7554/elife.51254 · Cited by 174 · see citing works
Hallstrom, T. C., & Moye-Rowley, W. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007338200 · Cited by 194 · see citing works
Mitohormesis in exercise training
Merry, T. L., & Ristow, M. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.11.032 · Cited by 176 · see citing works
The retrograde response: When mitochondrial quality control is not enough
Jazwinski, S. M. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.02.010 · Cited by 172 · see citing works
Kaur, R., Castaño, I., & Cormack, B. P. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.5.1600-1613.2004 · Cited by 167 · see citing works
Cristina, D., Cary, M., Lunceford, A., Clarke, C., & Kenyon, C. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000450 · Cited by 166 · see citing works
Pérez, J. C., Kumamoto, C. A., & Johnson, A. D. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001510 · Cited by 156 · see citing works
Retrograde signaling is regulated by the dynamic interaction between Rtg2p and Mks1p
Liu, Z., Sekito, T., Špı́rek, M., Thornton, J., & Butow, R. A. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00285-5 · Cited by 148 · see citing works
Self-citationDietary restriction.; mitochondrial function and aging: From yeast to humans
Ruetenik, A., & Barrientos, A. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.005 · Cited by 139 · see citing works
Rothermel, B. A., Thornton, J. L., & Butow, R. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.32.19801 · Cited by 112 · see citing works
Self-citationAup1-mediated regulation of Rtg3 during mitophagy
Journo, D., Mor, A., & Abeliovich, H. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.048140 · Cited by 90 · see citing works
Zhang, X., & Moye-Rowley, W. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106285200 · Cited by 84 · see citing works
Lim, J. H., Lee, J. I., Suh, Y. H., Kim, W., Song, J. H., & Jung, M. H. (2006) · Diabetologia · doi:10.1007/s00125-006-0278-4 · Cited by 81 · see citing works
Glucocorticoid and thyroid hormone receptors in mitochondria of animal cells
Scheller, K., Seibel, P., & Sekerist, C. E. (2003) · International review of cytology · doi:10.1016/s0074-7696(02)22011-2 · Cited by 73 · see citing works
Mitochondria-cytosol-nucleus crosstalk: learning from Saccharomyces cerevisiae
Guaragnella, N., Coyne, L. P., Chen, X. J., & Giannattasio, S. (2018) · FEMS Yeast Research · doi:10.1093/femsyr/foy088 · Cited by 72 · see citing works
Verma, S., Shakya, V. P. S., & Idnurm, A. (2018) · Virulence · doi:10.1080/21505594.2017.1414133 · Cited by 67 · see citing works
Jazwinski, S. M. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-394625-6.00005-2 · Cited by 67 · see citing works
Malecki, M., Kamrad, S., Ralser, M., & Bähler, J. (2020) · The EMBO Reports · doi:10.15252/embr.202050845 · Cited by 50 · see citing works
Torelli, N. Q., Ferreira-Júnior, J. R., Kowaltowski, A. J., & da Cunha, F. M. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.12.025 · Cited by 37 · see citing works
Moreno-Velásquez, S. D., Tint, S. H., del Olmo Toledo, V., Torsin, S., De, S., & Pérez, J. C. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.022 · Cited by 25 · see citing works
Adaptive responses to mitochondrial dysfunction in the ρ° Namalwa cell
Behan, Á., Doyle, S., & Farrell, M. (2005) · Mitochondrion · doi:10.1016/j.mito.2005.03.002 · Cited by 25 · see citing works
Yan, H., Zhao, Y., & Jiang, L. (2014) · FEMS Yeast Research · doi:10.1111/1567-1364.12148 · Cited by 25 · see citing works
Chae, M. S., & Nargang, F. E. (2009) · Physiologia Plantarum · doi:10.1111/j.1399-3054.2009.01239.x · Cited by 17 · see citing works
Dey, T., Krishna Rao, K., Khatun, J., & Rangarajan, P. N. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004486 · Cited by 16 · see citing works
Qi, Z., Smith, K. M., Bredeweg, E. L., Bosnjak, N., Freitag, M., & Nargang, F. E. (2017) · G3 Genes|Genomes|Genetics · doi:10.1534/g3.116.035402 · Cited by 12 · see citing works
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
- Liao, X., & Butow, R. A.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1993-01
- Volume
- 72
- Issue
- 1
- Pages
- 61-71
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2128525259
- Cited by
- 419
- References
- 1
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 13 · 2020: 8 · 2019: 9 · 2018: 12 · 2017: 19 · 2016: 16 · 2015: 11 · 2014: 10 · 2013: 12 · 2012: 10
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (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
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- retrograde regulation, bHLH transcription factors, mitochondrial-nuclear communication, peroxisomes, TCA cycle, glyoxylate cycle, auxotrophy, Saccharomyces cerevisiae
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cell Nucleus, Citrate (si)-Synthase, Cloning, Molecular, DNA-Binding Proteins, DNA, Fungal, Fungal Proteins, Genes, Fungal, Genes, Regulator, Glycerol, Microbodies, Mitochondria, Molecular Sequence Data, Mutation, Regulatory Sequences, Nucleic Acid, Saccharomyces cerevisiae, Transcription Factors, Gene Expression Regulation, Fungal, Sequence Homology, Amino Acid, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
