Temporal Regulation of Autophagy- and Mitophagy-related Genes in Saccharomyces cerevisiae under Gradual Glucose Restriction

Document Type : Research Article

Authors

1 Department of Biology, Hakim Sabzevari University, Sabzevar, Iran

2 University of Al- Hamdaniya, Education Faculty, Biology Department, Iraq

10.22080/jgr.2026.32509.1481

Abstract

Nutrient availability is widely recognized as a critical regulator of cellular homeostasis and metabolic adaptation. In this study, we investigated the transcriptional dynamics of autophagy- and mitophagy-related genes in Saccharomyces cerevisiae under graded glucose restriction (1%, 0.5%, and 0.2%), using a 2% glucose environment as the control. Growth kinetics, metabolic vitality, and qualitative survival profiles were systematically evaluated on days 5 and 7, corresponding to critical chronological transition phases. Additionally, relative mRNA expression levels of ATG8, ATG11, and ATG32 were quantified via qRT-PCR. On day 5, a pronounced, time-dependent metabolic surge was observed through MTT assays across all restricted environments, correlating with enhanced colony-forming efficiency in spotting assays. Concurrently, transcriptional analyses revealed that severe glucose restriction (0.2%) induced significant up-regulation of the mitophagy receptor ATG32 and the scaffold protein ATG11. Furthermore, a substantial down-regulation of the core autophagy marker ATG8 was simultaneously detected across all restricted groups, suggesting that decreased ATG8 expression may reflect an overall reduction in general autophagic activity, while the concurrent induction of ATG32 and ATG11 indicates a localized retention or activation of selective mitochondrial quality control under extreme restriction. This selective transcriptional response suggests that S. cerevisiae possesses an acute, temporary adaptive capacity. By day 7, however, metabolic activity and transcriptional profiles had returned toward a baseline maintenance levels, with expression differences becoming statistically comparable to the control. Notably, overall cellular viability was successfully preserved throughout these nutritional adjustments. Consequently, this study demonstrates that S. cerevisiae has an acute, temporary adaptive capacity, whereby its autophagic machinery can be dynamically recalibrated to optimize energy expenditure and selectively manage organelle quality under prolonged nutritional stress.

Keywords

Main Subjects

References

Abeliovich, H. (2023). Mitophagy in yeast: Known unknowns and unknown unknowns. Biochemical Journal, 480(20), 1639-1657. https://doi.org/10.1042/BCJ20230279
Aris, J. P., Alvers, A. L., Ferraiuolo, R. A., Fishwick, L. K., Hanvivatpong, A., Hu, D., … & Dunn Jr, W. A. (2013). Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast. Experimental Gerontology, 48(10), 1107-1119. https://doi.org/10.1016/j.exger.2013.01.006
Arlia-Ciommo, A., Leonov, A., Piano, A., Svistkova, V., & Titorenko, V. I. (2014). Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae. Microbial Cell, 1(6), 163-178. https://doi.org/10.15698/mic2014.06.152
Boutelle, K. N., Peterson, C. B., Crosby, R. D., Rydell, S. A., Zucker, N., & Harnack, L. (2014). Overeating phenotypes in overweight and obese children. Appetite, 76, 95-100. https://doi.org/10.1016/j.appet.2014.01.076
Burtner, C. R., Murakami, C. J., Kennedy, B. K., & Kaeberlein, M. (2009). A molecular mechanism of chronological aging in yeast. Cell Cycle, 8(8), 1256-1270. https://doi.org/10.4161/cc.8.8.8287
Camougrand, N., Vigie, P., Gonzalez, C., Manon, S., & Bhatia-Kissova, I. (2020). The yeast mitophagy receptor Atg32 is ubiquitinated and degraded by the proteasome. PLOS One, 15(12), e0241576. https://doi.org/10.1371/journal.pone.0241576
Delaney, J. R., Murakami, C., Chou, A., Carr, D., Schleit, J., Sutphin, G. L., … & Kaeberlein, M. (2013). Dietary restriction and mitochondrial function link replicative and chronological aging in Saccharomyces cerevisiae. Experimental Gerontology, 48(10), 1006-1013. https://doi.org/10.1016/j.exger.2012.12.001
Engel, S. R., Dietrich, F. S., Fisk, D. G., Binkley, G., Balakrishnan, R., Costanzo, M. C., … & Cherry, J. M. (2014). The reference genome sequence of Saccharomyces cerevisiae: Then and now. G3: Genes, Genomes, Genetics, 4(3), 389-398. https://doi.org/10.1534/g3.113.008995
Hill, L., Guyot, S., Bertheau, L., & Davey, H. (2024). Calorie restriction decreases competitive fitness in Saccharomyces cerevisiae following heat stress. Microorganisms, 12(9), 1838. https://doi.org/10.3390/microorganisms12091838
Hoshyar-Chamanarae, H., & Moghaddam, M. M. (2024). Major genes involved in mitophagy of Saccharomyces cerevisiae. Journal of Cell and Molecular Research, 15(2), 89. https://doi.org/10.22067/jcmr.2024.103986
Hossain, M. J., Al-Mamun, M., & Islam, M. R. (2024). Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused. Health Science Reports, 7(3), e2004. https://doi.org/10.1002/hsr2.2004
Innokentev, A., & Kanki, T. (2021). Mitophagy in yeast: Molecular mechanism and regulation. Cells, 10(12), 3569. https://doi.org/10.3390/cells10123569
Jarolim, S., Millen, J., Heeren, G., Laun, P., Goldfarb, D. S., & Breitenbach, M. (2004). A novel assay for replicative lifespan in Saccharomyces cerevisiae. Federation of European Microbiological Societies Yeast Research, 5(2), 169-177. https://doi.org/10.1016/j.femsyr.2004.06.015
Jazwinski, S. M. (2005). Yeast longevity and aging-the mitochondrial connection. Mechanisms of Ageing and Development, 126(2), 243-248. https://doi.org/10.1016/j.mad.2004.08.016
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., … & Tong, C. K. (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy, 17(1), 1-382. https://doi.org/10.1080/15548627.2020.1797280
Kohli, L., & Roth, K. A. (2010). Autophagy: Cerebral home cooking. American Journal of Pathology, 176(3), 1065-1071. https://doi.org/10.2353/ajpath.2010.090850
Kyryakov, P., Beach, A., Richard, V. R., Burstein, M. T., Leonov, A., Levy, S., & Titorenko, V. I. (2012). Caloric restriction extends yeast chronological lifespan by altering a pattern of age-related changes in trehalose concentration. Frontiers in Physiology, 3, 256. https://doi.org/10.3389/fphys.2012.00256
Liu, L., Li, Y., Chen, G., & Chen, Q. (2023). Crosstalk between mitochondrial biogenesis and mitophagy to maintain mitochondrial homeostasis. Journal of Biomedical Science, 30(1), 86. https://doi.org/10.1186/s12929-023-00975-7
Longo, V. (2019). The longevity diet: Slow aging, fight disease, optimize weight. Avery
Longo, V. D., & Fabrizio, P. (2012). Chronological aging in Saccharomyces cerevisiae. Aging Research in Yeast, 57, 101-121. https://doi.org/10.1007/978-94-007-2561-4_5
Longo, V. D., Shadel, G. S., Kaeberlein, M., & Kennedy, B. (2012). Replicative and chronological aging in Saccharomyces cerevisiae. Cell Metabolism, 16(1), 18-31. https://doi.org/10.1016/j.cmet.2012.06.002
Madhusudhanan, J., Suresh, G., & Devanathan, V. (2020). Neurodegeneration in type 2 diabetes: Alzheimer's as a case study. Brain and Behavior, 10(5), e01577. https://doi.org/10.1002/brb3.1577
McCleary, D. F., & Rine, J. (2017). Nutritional control of chronological aging and heterochromatin in Saccharomyces cerevisiae. Genetics, 205(3), 1179-1193. https://doi.org/10.1534/genetics.116.196485
Mirisola, M. G., & Longo, V. D. (2022). Yeast chronological lifespan: Longevity regulatory genes and mechanisms. Cells, 11(10), 1714. https://doi.org/10.3390/cells11101714
Mizushima, N., & Komatsu, M. (2011). Autophagy: Renovation of cells and tissues. Cell, 147(4), 728-741. https://doi.org/10.1016/j.cell.2011.10.026
Mortimer, R. K., & Johnston, J. R. (1959). Life span of individual yeast cells. Nature, 183(4677), 1751-1752. https://doi.org/10.1038/1831751a0
Olivares-Marin, I. K., Gonzalez-Hernandez, J. C., Regalado-Gonzalez, C., & Madrigal-Perez, L. A. (2018). Saccharomyces cerevisiae exponential growth kinetics in batch culture to analyze respiratory and fermentative metabolism. Journal of Visualized Experiments, 2018(139), 58192. https://doi.org/10.3791/58192
Osellame, L. D., Blacker, T. S., & Duchen, M. R. (2012). Cellular and molecular mechanisms of mitochondrial function. Best Practice and Research Clinical Endocrinology and Metabolism, 26(6), 711-723. https://doi.org/10.1016/j.beem.2012.05.003
Pan, Y. (2011). Mitochondria, reactive oxygen species, and chronological aging: A message from yeast. Experimental Gerontology, 46(11), 847-852. https://doi.org/10.1016/j.exger.2011.08.007
Parrella, E., & Longo, V. D. (2008). The chronological life span of Saccharomyces cerevisiae to study mitochondrial dysfunction and disease. Methods, 46(4), 256-262. https://doi.org/10.1016/j.ymeth.2008.10.004
Pignatti, C., D’Adamo, S., Stefanelli, C., Flamigni, F., & Cetrullo, S. (2020). Nutrients and pathways that regulate health span and life span. Geriatrics, 5(4), 95. https://doi.org/10.3390/geriatrics5040095
Sampaio-Marques, B., Burhans, W. C., & Ludovico, P. (2014). Longevity pathways and maintenance of the proteome: The role of autophagy and mitophagy during yeast ageing. Microbial Cell, 1(4), 118-127. https://doi.org/10.15698/mic2014.04.136
Sampaio-Marques, B., Felgueiras, C., Silva, A., Rodrigues, F., & Ludovico, P. (2011). Yeast chronological lifespan and proteotoxic stress: Is autophagy good or bad? Biochemical Society Transactions, 39(5), 1466-1470. https://doi.org/10.1042/BST0391466
Schulze, A., Zimmermann, A., Kainz, K., Egger, N. B., Bauer, M. A., Madeo, F., & Carmona-Gutierrez, D. (2024). Assessing chronological aging in Saccharomyces cerevisiae. Methods in Cell Biology, 181, 87-108. https://doi.org/10.1016/bs.mcb.2022.09.006
Schwartz, M. B., & Puhl, R. (2003). Childhood obesity: A societal problem to solve. Obesity Reviews, 4(1), 57-71. https://doi.org/10.1046/j.1467-789X.2003.00093.x
Swinnen, E., Ghillebert, R., Wilms, T., & Winderickx, J. (2014). Molecular mechanisms linking the evolutionary conserved TORC1-Sch9 nutrient signalling branch to lifespan regulation in Saccharomyces cerevisiae. Federation of European Microbiological Societies Yeast Research, 14(1), 17-32. https://doi.org/10.1111/1567-1364.12097
Vasile, C. M., Padovani, P., Rujinski, S. D., Nicolosu, D., Toma, C., Turcu, A. A., & Cioboata, R. (2023). The increase in childhood obesity and its association with hypertension during pandemics. Journal of Clinical Medicine, 12(18), 5909. https://doi.org/10.3390/jcm12185909
Journal of Genetic Resources
Volume 12, Issue 2
In Progress
2026
Pages 206-219

Files

Share

How to cite

Statistics