KaydedilenlerDerginizi ekleyin

Dergiler / Trakya University Journal of Natural Sciences / 2026 / Volume: 27 Issue: 2

Role of yeast MIG1 gene in glycolysis, mitochondrial bioenergetics, and glycogen and trehalose biosynthesis in response to DNA damage

Van Ngoc Bui(Institute of Biology (IB), Vietnam Academy of Science and Technology)0000-0002-4659-7338
Duc Duy Nguyen(Institute of Biology (IB), Vietnam Academy of Science and Technolog)0009-0006-9969-1148
Hong Phuc Cao(Institute of Biology (IB), Vietnam Academy of Science and Technology)0000-0002-8824-6894
Trung Hieu Bui(Nguyen Tat Thanh University Center for Hi-Tech Development, Saigon Hi-Tech Park)0000-0002-1103-5845
Hoang Ha Chu(Institute of Biology (IB), Vietnam Academy of Science and Technology)0009-0000-7220-2232
Thi Thu Huyen Nguyen(Faculty of Natural Science and Technology, Thai Nguyen University of Sciences)0009-0005-9033-6783
Sayfa
—
Yayın Tarihi
2026-10-15
🏛️Bu makalenin bibliyografik verileri ve tam metin bağlantısı DergiPark üzerinden sağlanmıştır.
DergiPark Kaydı ↗
✨

Yapay Zeka Hızlı Bakış & Çıkarımlar

AI Insight
⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

These reserve carbohydrates act as readily mobilized storage form of glucose for cell survival of the ∆mig1 mutant cells.

📌 3 Maddede Bu Makale

🎯
Amaç & Hipotez:Background: In eukaryotic cells, under certain stress conditions, the diversion of carbohydrate flux, either downstream toward tricarboxylic acid (TCA) cycle or upstream toward the hexosamine biosynthesis and pentose phosphate pathways, is governed by the activation of key regulatory genes and glycolytic enzymes.
📊
Temel Bulgular & Veri:In Saccharomyces cerevisiae, the transcription factor Mig1 (encoded by the MIG1 gene) regulates respiration, glucose repression, and gluconeogenesis.
💡
Sonuç & Katkı:These reserve carbohydrates act as readily mobilized storage form of glucose for cell survival of the ∆mig1 mutant cells.
🔬Tür:Research Article
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:DNA damage · glycogen · glycolysis

Abstract

Background: In eukaryotic cells, under certain stress conditions, the diversion of carbohydrate flux, either downstream toward tricarboxylic acid (TCA) cycle or upstream toward the hexosamine biosynthesis and pentose phosphate pathways, is governed by the activation of key regulatory genes and glycolytic enzymes. In Saccharomyces cerevisiae, the transcription factor Mig1 (encoded by the MIG1 gene) regulates respiration, glucose repression, and gluconeogenesis. In addition, Mig1 pathway represses Hap2p/3p/4p/5p complex, thereby modulating genes involved in the TCA cycle and mitochondrial electron transport chain. Aims: This study aimed to investigate the role of the MIG1 gene in regulating glycolysis, mitochondrial bioenergetics/respiration, and reserve carbohydrate biosynthesis in response to DNA damage. Methods: The wild type (BY4742) and specific knock-out (∆mig1) Saccharomyces cerevisiae strains were treated with methyl methanesulfonate (MMS) to induce DNA damage. Cellular responses were analyzed by using flow cytometry, chromatography, OxoPlate®, gloxo, and enzymatic assays. Results : The deletion of MIG1 fundamentally impaired the mitochondrial electron transport chain and reduced oxygen consumption, which rendered the Δmig1 mutant highly susceptible to MMS-induced genotoxic stress. This deficiency triggered an elevated accumulation of reactive oxygen species (ROS), which associated with inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pyruvate kinase (PYK) activities, thereby decreasing downstream ATP production. To counteract this energy crisis and support cellular signaling during the DNA damage response, carbohydrate flux bypassed standard glycolysis and the TCA cycle. Instead, glucose was redirected upstream toward the pentose phosphate pathway via enhanced glucose-6-phosphate dehydrogenase (G6PDH) activity, shunted into the hexosamine biosynthesis pathway to yield elevated uridine diphosphate N-acetylglucosamine (UDP-NacGlu) levels, and ultimately diverted into gluconeogenesis or storage as glycogen and trehalose reserves. Conclusion: MMS-treated ∆mig1 cells promoted glycogen and trehalose synthesis more intensively than the MMS-treated wild type. These reserve carbohydrates act as readily mobilized storage form of glucose for cell survival of the ∆mig1 mutant cells.

🔖

Bu Makaleye Atıf Yap

Bui, V. N., Nguyen, D. D., Cao, H. P., Bui, T. H., Chu, H. H., Nguyen, T. T. H. (2026). Role of yeast MIG1 gene in glycolysis, mitochondrial bioenergetics, and glycogen and trehalose biosynthesis in response to DNA damage. Trakya University Journal of Natural Sciences, Volume: 27 Issue: 2. https://doi.org/10.23902/trkjnat.2045953

📄 Tam Metin PDF Okuyucu

📄

PDF görüntüleyici hazırlanıyor...

Kaynakça (55)

  1. An, X., Yu, L., Wang, S., Ao, Y., Zhan, X., Liu, Q., Zhao, Y., Li, M., Shu, X., & Li, F. (2021). Kinetic characterization and inhibitor screening of pyruvate kinase I from Babesia microti. Frontiers in Microbiology, 12, 710678. https://doi.org/10.3389/fmicb.2021.710678
  2. Atkinson, D. E. (1968). Energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry, 7(11), 4030–4034. https://doi.org/10.1021/bi00851a033
  3. Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002). Glycolysis is an energy-conversion pathway in many organisms. Biochemistry (pp. 433–434). 5th Ed. New York: WH Freeman.
  4. Bonowski, F., Kitanovic, A., Ruoff, P., Holzwarth, J., Kitanovic, I., Ngoc Bui, V., Lederer, E., & Wölfl, S. (2010). Computer controlled automated assay for comprehensive studies of enzyme kinetic parameters. PLoS One, 5(5), e10727. https://doi.org/10.1371/journal.pone.0010727
  5. Bui, V. N., Nguyen, T. P. T., Nguyen, H. D., Phi, Q. T., Nguyen, T. N., & Chu, H. H. (2024). Bioactivity responses to changes in mucus-associated bacterial composition between healthy and bleached Porites lobata corals. Journal of Invertebrate Pathology, 206, 108164. https://doi.org/10.1016/j.jip.2024.108164
  6. Bui, V. N., Nguyen, T. T., Bettarel, Y., Nguyen, T. H., Pham, T. L., Hoang, T. Y., Nguyen, V. T., Nghiem, N. M., & Wolfl, S. (2015). Genotoxicity of chemical compounds identification and assessment by yeast cells transformed with GFP reporter constructs regulated by the PLM2 or DIN7 promoter. International Journal of Toxicology, 34(1), 31–43. https://doi.org/10.1177/1091581814566870
  7. Bui, V. N., Nguyen, T. T., Mai, C. T., Bettarel, Y., Hoang, T. Y., Trinh, T. T., Truong, N. H., Chu, H. H., Nguyen, V. T., Nguyen, H. D., & Wolfl, S. (2016). Procarcinogens - Determination and evaluation by yeast-based biosensor transformed with plasmids incorporating RAD54 reporter construct and cytochrome P450 genes. PloS One, 11(12), e0168721. https://doi.org/10.1371/journal.pone.0168721
  8. Capps, D., Hunter, A., Chiang, M., Pracheil, T., & Liu, Z. (2022). Ubiquitin-conjugating enzymes Ubc1 and Ubc4 mediate the turnover of Hap4, a master regulator of mitochondrial biogenesis in Saccharomyces cerevisiae. Microorganisms, 10(12), 2370. https://doi.org/10.3390/microorganisms10122370
  9. Carrillo-Garmendia, A., Martinez-Ortiz, C., Martinez-Garfias, J. G., Suarez-Sandoval, S. E., González-Hernández, J. C., Nava, G. M., Dufoo-Hurtado, M. D., & Madrigal-Perez, L. A. (2022). Snf1p/Hxk2p/Mig1p pathway regulates hexose transporters transcript levels, affecting the exponential growth and mitochondrial respiration of Saccharomyces cerevisiae. Fungal Genetics and Biology, 161, 103701. https://doi.org/10.1016/j.fgb.2022.103701
  10. Chenna, S., Koopman, W. J. H., Prehn, J. H. M., & Connolly, N. M. C. (2022). Mechanisms and mathematical modeling of ROS production by the mitochondrial electron transport chain. American Journal of Physiology-Cell Physiology, 323(1), C69–C83. https://doi.org/10.1152/ajpcell.00455.2021
  11. Coustou, V., Besteiro, S., Biran, M., Diolez, P., Bouchaud, V., Voisin, P., Michels, P. A., Canioni, P., Baltz, T., & Bringaud, F. (2003). ATP generation in the Trypanosoma brucei procyclic form: Cytosolic substrate level phosphorylation is essential, but not oxidative phosphorylation. Journal of Biological Chemistry, 278(49), 49625–49635. https://doi.org/10.1074/jbc.M307872200
  12. Elbein, A. D. (2010). Cytoplasmic carbohydrate molecules: Trehalose and glycogen. Otto Holst, Patrick J. Brennan, Mark von Itzstein, Anthony P. Moran (Eds), Microbial Glycobiology (pp. 185–201). Academic Press
  13. François, J., & Parrou, J. L. (2001). Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae. Fems Microbiology Reviews, 25(1), 125–145. https://doi.org/10.1111/j.1574-6976.2001.tb00574.x
  14. Gomes, A. M., Orlandi, A. C. A., & Parachin, N. S. (2020). Deletion of the trehalose tps1 gene in Kluyveromyces lactis does not impair growth in glucose. FEMS Microbiology Letters, 367(10), fnaa072. https://doi.org/10.1093/femsle/fnaa072
  15. Groth, P., Ausländer, S., Majumder, M. M., Schultz, N., Johansson, F., Petermann, E., & Helleday, T. (2010). Methylated DNA causes a physical block to replication forks independently of damage signalling, O6-methylguanine or DNA single-strand breaks and results in DNA damage. Journal of Molecular Biology, 402(1), 70–82. https://doi.org/10.1016/j.jmb.2010.07.010
  16. Halim, A., Larsen, I. S. B., Neubert, P., Joshi, H. J., Petersen, B. L., Vakhrushev, S. Y., Strahl, S., & Clausen, H. (2015). Discovery of a nucleocytoplasmic O-mannose glycoproteome in yeast. Proceedings of the National Academy of Sciences, 112(51), 15648–15653. https://doi.org/10.1073/pnas.1511743112
  17. Hara, M. R., Thomas, B., Cascio, M. B., Bae, B.-I., Hester, L. D., Dawson, V. L., Dawson, T. M., Sawa, A., & Snyder, S. H. (2006). Neuroprotection by pharmacologic blockade of the GAPDH death cascade. Proceedings of the National Academy of Sciences, 103(10), 3887–3889. https://doi.org/10.1073/pnas.0511321103
  18. Jin, J., Wang, X., Wang, J., Li, K., Wang, S., Zhang, W., Zhang, G., & Bi, Y. (2021). Glucose-6-phosphate dehydrogenase is involved in the tolerance of soybean seedlings to low nitrogen stress. Agronomy, 11(4), 637.
  19. Kawai, K., Kanesaki, Y., Yoshikawa, H., & Hirasawa, T. (2019). Identification of metabolic engineering targets for improving glycerol assimilation ability of Saccharomyces cerevisiae based on adaptive laboratory evolution and transcriptome analysis. Journal of Bioscience and Bioengineering, 128(2), 162–169. https://doi.org/10.1016/j.jbiosc.2019.02.001
  20. Kitanovic, A., Walther, T., Loret, M. O., Holzwarth, J., Kitanovic, I., Bonowski, F., Van Bui, N., Francois, J. M., & Wölfl, S. (2009). Metabolic response to MMS-mediated DNA damage in Saccharomyces cerevisiae is dependent on the glucose concentration in the medium. FEMS Yeast Research, 9(4), 535–551. https://doi.org/10.1111/j.1567-1364.2009.00505.x
  21. Lapshina, E. A., Sudnikovich, E. J., Maksimchik, J. Z., Zabrodskaya, S. V., Zavodnik, L. B., Kubyshin, V. L., Nocun, M., Kazmierczak, P., Dobaczewski, M., & Watala, C. (2006). Antioxidative enzyme and glutathione S-transferase activities in diabetic rats exposed to long-term ASA treatment. Life Sciences, 79(19), 1804–1811. https://doi.org/10.1016/j.lfs.2006.06.008
  22. Lesko, M. A., Chandrashekarappa, D. G., Jordahl, E. M., Oppenheimer, K. G., Bowman, R. W., Shang, C., Durrant, J. D., Schmidt, M. C., & O’Donnell, A. F. (2023). Changing course: Glucose starvation drives nuclear accumulation of Hexokinase 2 in S. cerevisiae. PLoS Genetics, 19(5), e1010745. https://doi.org/10.1371/journal.pgen.1010745
  23. Lillie, S. H., & Pringle, J. R. (1980). Reserve carbohydrate metabolism in Saccharomyces cerevisiae: Responses to nutrient limitation. Journal of Bacteriology, 143(3), 1384–1394. https://doi.org/10.1128/jb.143.3.1384-1394.1980
  24. Loret, M. O., Pedersen, L., & François, J. (2007). Revised procedures for yeast metabolites extraction: Application to a glucose pulse to carbon‐limited yeast cultures, which reveals a transient activation of the purine salvage pathway. Yeast, 24(1), 47–60. https://doi.org/10.1002/yea.1435
  25. Lu, Z., Shen, Q., Liu, L., Talbo, G., Speight, R., Trau, M., Dumsday, G., Howard, C. B., Vickers, C. E., & Peng, B. (2023). Profiling proteomic responses to hexokinase-II depletion in terpene-producing Saccharomyces cerevisiae. Engineering Microbiology, 3(3), 100079. https://doi.org/10.1016/j.engmic.2023.100079
  26. Lunn, J. E., Delorge, I., Figueroa, C. M., Van Dijck, P., & Stitt, M. (2014). Trehalose metabolism in plants. The Plant Journal, 79(4), 544–567. https://doi.org/10.1111/tpj.12509
  27. Ma, J., Wei, K., Liu, J., Tang, K., Zhang, H., Zhu, L., Chen, J., Li, F., Xu, P., & Chen, J. (2020). Glycogen metabolism regulates macrophage-mediated acute inflammatory responses. Nature Communications, 11(1), 1769. https://doi.org/10.1038/s41467-020-15636-8
  28. Marín-Hernández, A., Gallardo-Pérez, J. C., López-Ramírez, S. Y., García-García, J. D., Rodríguez-Zavala, J. S., Ruiz-Ramírez, L., Gracia-Mora, I., Zentella-Dehesa, A., Sosa-Garrocho, M., Macías-Silva, M., Moreno-Sánchez, R., & Rodríguez-Enríquez, S. (2012). Casiopeina II-gly and bromo-pyruvate inhibition of tumor hexokinase, glycolysis, and oxidative phosphorylation. Archives of Toxicology, 86(5), 753–766. https://doi.org/10.1007/s00204-012-0809-3
  29. Marín-Hernández, Á., Rodríguez-Zavala, J. S., Del Mazo-Monsalvo, I., Rodríguez-Enríquez, S., Moreno-Sánchez, R., & Saavedra, E. (2016). Inhibition of non-flux-controlling enzymes deters cancer glycolysis by accumulation of regulatory metabolites of controlling steps. Frontiers in Physiology, 7, 412. https://doi.org/10.3389/fphys.2016.00412
  30. Masi, A., Mach, R. L., & Mach-Aigner, A. R. (2021). The pentose phosphate pathway in industrially relevant fungi: crucial insights for bioprocessing. Applied Microbiology and Biotechnology, 105(10), 4017–4031. https://doi.org/10.1007/s00253-021-11314-x
  31. Parrou, J. L., Teste, M.-A., & François, J. (1997). Effects of various types of stress on the metabolism of reserve carbohydrates in Saccharomyces cerevisiae: Genetic evidence for a stress-induced recycling of glycogen and trehalose. Microbiology, 143(6), 1891–1900. https://doi.org/10.1099/00221287-143-6-1891
  32. Peeters, K., & Thevelein, J. M. (2014). Glucose sensing and signal transduction in Saccharomyces cerevisiae. In J. Piškur & C. Compagno (Eds), Molecular Mechanisms in Yeast Carbon Metabolism (pp. 21–56). Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-642-55013-3_2
  33. Pompon, D. (1999). Yeast physiology and biotechnology. Biofutur, 189(1999), 45.
  34. Preiss, J. (2014). Glycogen: Biosynthesis and regulation. EcoSal Plus, 6(1). https://doi.org/10.1128/ecosalplus.esp-0015-2014
  35. Qiu, Y., Wu, M., Bao, H., Liu, W., & Shen, Y. (2023). Engineering of Saccharomyces cerevisiae for co-fermentation of glucose and xylose: Current state and perspectives. Engineering Microbiology, 3(3), 100084. https://doi.org/10.1016/j.engmic.2023.100084
  36. Ralser, M., Wamelink, M. M., Kowald, A., Gerisch, B., Heeren, G., Struys, E. A., Klipp, E., Jakobs, C., Breitenbach, M., Lehrach, H., & Krobitsch, S. (2007). Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress. Journal of Biology, 6(4), 10. https://doi.org/10.1186/jbiol61
  37. Ritter, J. B., Genzel, Y., & Reichl, U. (2006). High-performance anion-exchange chromatography using on-line electrolytic eluent generation for the determination of more than 25 intermediates from energy metabolism of mammalian cells in culture. Journal of Chromatography B, 843(2), 216–226. https://doi.org/10.1016/j.jchromb.2006.06.004
  38. Saliola, M., Tramonti, A., Lanini, C., Cialfi, S., De Biase, D., & Falcone, C. (2012). Intracellular NADPH levels affect the oligomeric state of the glucose 6-phosphate dehydrogenase. Eukaryotic Cell, 11(12), 1503–1511. https://doi.org/10.1128/EC.00211-12
  39. Schüller, H.-J. (2003). Transcriptional control of nonfermentative metabolism in the yeast Saccharomyces cerevisiae. Current Genetics, 43(3), 139–160. https://doi.org/10.1007/s00294-003-0381-8
  40. Schwarz, L. V., Sandri, F. K., Scariot, F., Delamare, A. P. L., Valera, M. J., Carrau, F., & Echeverrigaray, S. (2023). High nitrogen concentration causes G2/M arrest in Hanseniaspora vineae. Yeast, 40(12), 640–650. https://doi.org/10.1002/yea.3911
  41. Shokolenko, I., Venediktova, N., Bochkareva, A., Wilson, G. L., & Alexeyev, M. F. (2009). Oxidative stress induces degradation of mitochondrial DNA. Nucleic Acids Research, 37(8), 2539–2548. https://doi.org/10.1093/nar/gkp100
  42. Tellis, M. B., Kotkar, H. M., & Joshi, R. S. (2023). Regulation of trehalose metabolism in insects: From genes to the metabolite window. Glycobiology, 33(4), 262–273. https://doi.org/10.1093/glycob/cwad011
  43. Valderrama, R., Corpas, F. J., Carreras, A., Gómez‐Rodríguez, M. V., Chaki, M., Pedrajas, J. R., Fernández‐Ocaña, A., Del Río, L. A., & Barroso, J. B. (2006). The dehydrogenase‐mediated recycling of NADPH is a key antioxidant system against salt‐induced oxidative stress in olive plants. Plant, Cell & Environment, 29(7), 1449–1459. https://doi.org/10.1111/j.1365-3040.2006.01530.x
  44. Van Houten, B., Woshner, V., & Santos, J. H. (2006). Role of mitochondrial DNA in toxic responses to oxidative stress. DNA Repair, 5(2), 145–152. https://doi.org/10.1016/j.dnarep.2005.03.002
  45. Vigetti, D., Viola, M., Karousou, E., De Luca, G., & Passi, A. (2014). Metabolic control of hyaluronan synthases. Matrix Biology, 35, 8–13. https://doi.org/10.1016/j.matbio.2013.10.002
  46. Virgilio, S., Cupertino, F. B., Ambrosio, D. L., & Bertolini, M. C. (2017). Regulation of the reserve carbohydrate metabolism by alkaline pH and calcium in Neurospora crassa reveals a possible cross-regulation of both signaling pathways. BMC Genomics, 18(1), 457. https://doi.org/10.1186/s12864-017-3832-1
  47. Volke, D. C., Olavarría, K., & Nikel, P. I. (2021). Cofactor specificity of glucose-6-phosphate dehydrogenase isozymes in Pseudomonas putida reveals a general principle underlying glycolytic strategies in bacteria. mSystems, 6(2), 10.1128/msystems.00014-21. https://doi.org/10.1128/msystems.00014-21
  48. Watanabe, D., Zhou, Y., Hirata, A., Sugimoto, Y., Takagi, K., Akao, T., Ohya, Y., Takagi, H., & Shimoi, H. (2016). Inhibitory role of greatwall-like protein kinase Rim15p in alcoholic fermentation via upregulating the UDP-glucose synthesis pathway in Saccharomyces cerevisiae. Applied and Environmental Microbiology, 82(1), 340–351. https://doi.org/10.1128/AEM.02977-15
  49. Wei, X., Chi, Z., Liu, G.-L., Hu, Z., & Chi, Z.-M. (2021). The genome-wide mutation shows the importance of cell wall integrity in growth of the psychrophilic yeast Metschnikowia australis W7-5 at different temperatures. Microbial Ecology, 81(1), 52–66. https://doi.org/10.1007/s00248-020-01577-8
  50. Whalley, N. A., Walters, S., & Hammond, K. (2008). Molecular Cell Biology. In B. Mendelow, M. Ramsay, N. Chetty, & W. Stevens (Eds.), Molecular Medicine for Clinicians (pp. 37–49). chapter, Wits University Press.
  51. Wilson, W. A., Roach, P. J., Montero, M., Baroja-Fernández, E., Muñoz, F. J., Eydallin, G., Viale, A. M., & Pozueta-Romero, J. (2010). Regulation of glycogen metabolism in yeast and bacteria. FEMS Microbiology Reviews, 34(6), 952–985. https://doi.org/10.1111/j.1574-6976.2010.00220.x
  52. Yang, Y., Gordenin, D. A., & Resnick, M. A. (2010). A single-strand specific lesion drives MMS-induced hyper-mutability at a double-strand break in yeast. DNA Repair, 9(8), 914–921. https://doi.org/10.1016/j.dnarep.2010.06.005
  53. Yang, Y., Yao, Y., Li, J., Zhang, J., Zhang, X., Hu, L., Ding, D., Bakpa, E. P., & Xie, J. (2022). Trehalose alleviated salt stress in tomato by regulating ROS metabolism, photosynthesis, osmolyte synthesis, and trehalose metabolic pathways. Frontiers in Plant Science, 13, 772948. https://doi.org/10.3389/fpls.2022.772948
  54. Yao Y., Tsuchiyama S., Yang C., Bulteau A. L., He C., Robison B., Tsuchiya M., Miller D., Briones V., Tar K., Potrero A., Friguet B., Kennedy B. K., & Schmidt M. (2015). Proteasomes, Sir2, and Hxk2 form an interconnected aging network that impinges on the AMPK/Snf1-regulated transcriptional repressor Mig1. PLoS Genet, 11(1): e1004968. https://doi.org/10.1371/journal.pgen.1004968
  55. Yap, C. F., Garcia-Albornoz, M., Jarnuczak, A. F., Hubbard, S. J., & Schwartz, J.-M. (2021). Model parameterization with quantitative proteomics: Case study with trehalose metabolism in Saccharomyces cerevisiae. Processes, 9(1), 139.