Effects of Aluminum Exposure and Involvement of Tor1 Signaling on Cell Cycle Regulation in Schizosaccharomyces pombe
Keywords:
aluminum toxicity, cell cycle, fission yeast, Tor1 signaling pathway.Abstract
Yeast cells are used as a model organism for determining biological and molecular mechanisms that control responses to environmental stress, such as heavy metals, as they share high similarity with higher eukaryotic organisms, including animals and humans. This study was conducted to investigate the effects of AlCl3 toxicity on wild-type and Target of Rapamycin knockout (ΔTor1) strains of Schizosaccharomyces pombe growth and cell cycle to explore the likely roles of the Tor1 signaling pathway in mediating Al toxicity. The growth of yeast cells was assessed through measuring cell density in media with serially increasing concentrations of AlCl3 in culture media at 3 h intervals. Yeast cells were cultured in liquid media containing 0, 750, and 1500 µM of AlCl3 for 3 and 6 h. Increasing concentrations of AlCl3 reduced the growth rate of both wild type and ΔTor1 strains in the same pattern; however ΔTor1 strain grew better in solid media at high AlCl3 concentration. The expression of the cdc2 gene was higher in ΔTor1 compared to wild type. The results of the current work demonstrate the likely involvement of the Tor1 signaling pathway in Al-induced effects on S. pombe cell cycle regulation.
References
Tang, J., Zhang, J., Ren, L., Zhou, Y., Gao, J., Luo, L., et al. Diagnosis of soil contamination using microbiological indices: a review on heavy metal pollution. Journal of Environmental Management. 2019; 242:121-30.
Kondaiah, G., Srineetha, U., Kumar, D. V. N., Rao, C. N., Aluminium Toxicity Affects Different Organisms: A Mini Review. Uttar Pradesh Journal of Zoology. 2024;45(16):64-73.
Rengel, Z., Aluminium cycling in the soil-plant-animal-human continuum. Biometals. 2004;17:669-89.
Rounds, M. A., Larsen, P. B., Aluminum-dependent root-growth inhibition in Arabidopsis results from AtATR-regulated cell-cycle arrest. Current Biology. 2008;18(19):1495-500.
Nezames, C. D., Sjogren, C. A., Barajas, J. F., Larsen, P. B., The Arabidopsis cell cycle checkpoint regulators TANMEI/ALT2 and ATR mediate the active process of aluminum-dependent root growth inhibition. The Plant Cell. 2012;24(2):608-21.
Chappard, D., Bizot, P., Mabilleau, G., Hubert, L., Aluminum and bone: Review of new clinical circumstances associated with Al3+ deposition in the calcified matrix of bone. Morphologie. 2016;100(329):95-105.
Touam, M., Martinez, F., Lacour, B., Bourdon, R., Zingraff, J., Di Giulio, S., et al. Aluminium-induced, reversible microcytic anemia in chronic renal failure: clinical and experimental studies. Clinical Nephrology. 1983;19(6):295-8.
Campbell, A., Bondy, S., Aluminum induced oxidative events and its relation to inflammation: a role for the metal in Alzheimer's disease. Cellular and molecular biology (Noisy-le-Grand, France). 2000;46(4):721-30.
Exley, C., The toxicity of aluminium in humans. Morphologie. 2016;100(329):51-5.
Vyas, A., Freitas, A. V., Ralston, Z. A., Tang, Z., Fission yeast Schizosaccharomyces pombe: a unicellular “micromammal” model organism. Current protocols. 2021;1(6):e151.
Wullschleger, S., Loewith, R., Hall, M. N., TOR signaling in growth and metabolism. Cell. 2006;124(3):471-84.
Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Current biology. 2004;14(14):1296-302.
Nakashima, A., Sato, T., Tamanoi, F., Fission yeast TORC1 regulates phosphorylation of ribosomal S6 proteins in response to nutrients and its activity is inhibited by rapamycin. Journal of cell science. 2010;123(5):777-86.
Valbuena, N., Rozalén, A. E., Moreno, S., Fission yeast TORC1 prevents eIF2α phosphorylation in response to nitrogen and amino acids via Gcn2 kinase. Journal of cell science. 2012;125(24):5955-9.
Gaubitz, C., Oliveira, T. M., Prouteau, M., Leitner, A., Karuppasamy, M., Konstantinidou, G., et al. Molecular basis of the rapamycin insensitivity of target of rapamycin complex 2. Molecular cell. 2015;58(6):977-88.
Betz, C., Hall, M. N., Where is mTOR and what is it doing there? Journal of Cell Biology. 2013;203(4):563-74.
Madrid, M., Vázquez-Marín, B., Franco, A., Soto, T., Vicente-Soler, J., Gacto, M., et al. Multiple crosstalk between TOR and the cell integrity MAPK signaling pathway in fission yeast. Scientific reports. 2016;6(1):37515.
Weisman, R., Cohen, A., Gasser, S. M., TORC 2—a new player in genome stability. EMBO molecular medicine. 2014;6(8):995-1002.
Forsburg, S. L., Rhind, N., Basic methods for fission yeast. Yeast. 2006;23(3):173-83.
Pfaffl, M. W., A new mathematical model for relative quantification in real-time RT–PCR. Nucleic acids research. 2001;29(9):e45-e.
Swaffer, M. P., Jones, A. W., Flynn, H. R., Snijders, A. P., Nurse, P., CDK substrate phosphorylation and ordering the cell cycle. Cell. 2016;167(7):1750-61. e16.
Fankhauser, C., Reymond, A., Cerutti, L., Utzig, S., Hofmann, K., Simanis, V., The S. pombe cdc15 gene is a key element in the reorganization of F-actin at mitosis. Cell. 1995;82(3):435-44.
Basu, S., Roberts, E. L., Jones, A. W., Swaffer, M. P., Snijders, A. P., Nurse, P., The hydrophobic patch directs cyclin B to centrosomes to promote global CDK phosphorylation at mitosis. Current Biology. 2020;30(5):883-92. e4.
Ikai, N., Nakazawa, N., Hayashi, T., Yanagida, M., The reverse, but coordinated, roles of Tor2 (TORC1) and Tor1 (TORC2) kinases for growth, cell cycle and separase-mediated mitosis in Schizosaccharomyces pombe. Open biology. 2011;1(3):110007.
Lu, L. X., Domingo-Sananes, M. R., Huzarska, M., Novak, B., Gould, K. L., Multisite phosphoregulation of Cdc25 activity refines the mitotic entrance and exit switches. Proceedings of the National Academy of Sciences. 2012;109(25):9899-904.
Požgajová, M., Navrátilová, A., Šebová, E., Kovár, M., Kačániová, M., Cadmium-induced cell homeostasis impairment is suppressed by the Tor1 deficiency in fission yeast. International Journal of Molecular Sciences. 2020;21(21):7847.
Navratilova, A., Kovar, M., Trakovicka, A., Pozgajova, M., Nickel induced cell impairments are negatively regulated by the Tor1 kinase in Schizosaccharomyces pombe. World Journal of Microbiology and Biotechnology. 2021;37(10):165.
Zheng, K., Pan, J.-W., Ye, L., Fu, Y., Peng, H.-Z., Wan, B.-Y., et al. Programmed cell death-involved aluminum toxicity in yeast alleviated by antiapoptotic members with decreased calcium signals. Plant physiology. 2007;143(1):38-49.
Navrátilová, A., Kovár, M., Klongová, L., Bakošová, A., Peťková, M., Požgajová, M., Acrylamide-mediated errors in the cell cycle regulation are associated with altered TORC2 signaling in Schizosaccharomyces pombe. Scientific Reports. 2025;15(1):35310.
