International Journal of Innovative Approaches in Science Research
Abbreviation: IJIASR | ISSN (Print): 2602-4810 | ISSN (Online): 2602-4535 | DOI: 10.29329/ijiasr

Review article    |    Open Access
International Journal of Innovative Approaches in Science Research 2019, Vol. 3(2) 41-52

Cellular responses of Saccharomyces cerevisiae Against Arsenic

Mert Metin & Özge Karakaş Metin

pp. 41 - 52   |  DOI:

Published online: June 28, 2019  |   Number of Views: 178  |  Number of Download: 762


Arsenic is a metalloid member of heavy metals associated with many health problems from various cancers to skin diseases. Due to mankind activities and natural sources, arsenic contamination seen globally. More than 150 million people globally face with arsenic via arsenic polluted ground water. It is well known that speciation of arsenic is important for its actions inside of the exposed organism. Saccharomyces cerevisiae, is one of six model organisms, provides an general answer for the question “What eukaryotes do?”. So assessing some questions on budding yeast gives a general idea about potential results in other eukaryotes including human. One of the issues investigated on this yeast is that impacts and metabolism of arsenic. Arsenic is well studied on Saccharomyces cerevisiae and consequently much data became available. In this review, cellular impacts of arsenic and response of the yeast towards arsenic exposure is covered.

Keywords: Saccharomyces cerevisiae, arsenic, signaling pathways, cytotoxicity, protein aggregation

How to Cite this Article

APA 6th edition
Metin, M. & Metin, O.K. (2019). Cellular responses of Saccharomyces cerevisiae Against Arsenic . International Journal of Innovative Approaches in Science Research, 3(2), 41-52. doi: 10.29329/ijiasr.2019.197.2

Metin, M. and Metin, O. (2019). Cellular responses of Saccharomyces cerevisiae Against Arsenic . International Journal of Innovative Approaches in Science Research, 3(2), pp. 41-52.

Chicago 16th edition
Metin, Mert and Ozge Karakas Metin (2019). "Cellular responses of Saccharomyces cerevisiae Against Arsenic ". International Journal of Innovative Approaches in Science Research 3 (2):41-52. doi:10.29329/ijiasr.2019.197.2.

  1. Aaltonen, E. K. J., & Silow, M. (2008). Transmembrane topology of the Acr3 family arsenite transporter from Bacillus subtilis. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1778(4), 963–973. [Google Scholar]
  2. Ahmadpour, D., Maciaszczyk‐Dziubinska, E., Babazadeh, R., Dahal, S., Migocka, M., Andersson, M., … Hohmann, S. (2016). The mitogen‐activated protein kinase Slt2 modulates arsenite transport through the aquaglyceroporin Fps1. FEBS Letters, 590(20), 3649–3659. [Google Scholar]
  3. Aposhian, H. V., & Aposhian, M. M. (2006). Arsenic toxicology: five questions. Chemical Research in Toxicology, 19(1), 1–15. [Google Scholar]
  4. Bánfalvi, G. (2011). Heavy metals, trace elements and their cellular effects. In Cellular effects of heavy metals (pp. 3–28). Springer. [Google Scholar]
  5. Bates, M. N., Smith, A. H., & Hopenhayn-Rich, C. (1992). Arsenic ingestion and internal cancers: a review. American Journal of Epidemiology, 135(5), 462–476. [Google Scholar]
  6. Batista-Nascimento, L., Toledano, M. B., Thiele, D. J., & Rodrigues-Pousada, C. (2013). Yeast protective response to arsenate involves the repression of the high affinity iron uptake system. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1833(5), 997–1005. [Google Scholar]
  7. Bhattacharya, P., Frisbie, S. H., Smith, E., Naidu, R., Jacks, G., & Sarkar, B. (2002). Arsenic in the environment: a global perspective. Handbook of Heavy Metals in the Environment. Marcell Dekker Inc., New York, 147–215. [Google Scholar]
  8. Bun-ya, M., Shikata, K., Nakade, S., Yompakdee, C., Harashima, S., & Oshima, Y. (1996). Two new genes, PHO86 and PHO87, involved in inorganic phosphate uptake in Saccharomyces cerevisiae. Current Genetics, 29(4), 344–351. [Google Scholar]
  9. Chen, C. J., Chen, C. W., Wu, M. M., & Kuo, T. L. (1992). Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water. British Journal of Cancer, 66(5), 888–892. [Google Scholar]
  10. Chu, H.-A., & Crawford-Brown, D. (2006). Inorganic Arsenic in Drinking Water and Bladder Cancer: A Meta-Analysis for Dose-Response Assessment. International Journal of Environmental Research and Public Health, 3(4), 316–322. [Google Scholar] [Crossref] 
  11. Cortés, P., Castrejón, V., Sampedro, J. G., & Uribe, S. (2000). Interactions of arsenate, sulfate and phosphate with yeast mitochondria. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1456(2–3), 67–76. [Google Scholar]
  12. Cunningham, K. W., & Fink, G. R. (1994). Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking PMC1, a homolog of plasma membrane Ca2+ ATPases. The Journal of Cell Biology, 124(3), 351–363. [Google Scholar]
  13. Da Silva, J. J. R. F., & Williams, R. J. P. (2001). The biological chemistry of the elements: the inorganic chemistry of life. Oxford University Press. [Google Scholar]
  14. Di, Y., & Tamás, M. J. (2007). Regulation of the arsenic-responsive transcription factor Yap8p involves the ubiquitin-proteasome pathway. Journal of Cell Science, 120(2), 256–264. [Google Scholar]
  15. Escoté, X., Zapater, M., Clotet, J., & Posas, F. (2004). Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1. Nature Cell Biology, 6(10), 997. [Google Scholar]
  16. Ferreira, R. T., Menezes, R. A., & Rodrigues-Pousada, C. (2015). E4-Ubiquitin ligase Ufd2 stabilizes Yap8 and modulates arsenic stress responses independent of the U-box motif. Biology Open, bio-010405. [Google Scholar]
  17. Ferreira, R. T., Silva, A. R. C., Pimentel, C., Batista-Nascimento, L., Rodrigues-Pousada, C., & Menezes, R. A. (2012). Arsenic stress elicits cytosolic Ca2+ bursts and Crz1 activation in Saccharomyces cerevisiae. Microbiology, 158(9), 2293–2302. [Google Scholar]
  18. Fu, H.-L., Meng, Y., Ordóñez, E., Villadangos, A. F., Bhattacharjee, H., Gill, J. A., … Rosen, B. P. (2009). Properties of arsenite efflux permeases (Acr3) from Alkaliphilus metalliredigens and Corynebacterium glutamicum. Journal of Biological Chemistry, jbc-M109. [Google Scholar]
  19. Ghosh, M., Shen, J., & Rosen, B. P. (1999). Pathways of As (III) detoxification in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences, 96(9), 5001–5006. [Google Scholar]
  20. Goldberg, A. L. (2003). Protein degradation and protection against misfolded or damaged proteins. Nature, 426(6968), 895. [Google Scholar]
  21. González-Novo, A., Jiménez, J., Clotet, J., Nadal-Ribelles, M., Cavero, S., de Nadal, E., & Posas, F. (2015). Hog1 targets Whi5 and Msa1 transcription factors to down-regulate cyclin expression upon stress. Molecular and Cellular Biology, MCB-01279. [Google Scholar]
  22. Halem, D., Bakker, S. A., Amy, G., & Dijk, J. (2009). Arsenic in drinking water: A worldwide water quality concern for water supply companies. Drinking Water Engineering and Science (Vol. 2). [Google Scholar] [Crossref] 
  23. Haugen, A. C., Kelley, R., Collins, J. B., Tucker, C. J., Deng, C., Afshari, C. A., … Van Houten, B. (2004). Integrating phenotypic and expression profiles to map arsenic-response networks. Genome Biology, 5(12), R95. [Google Scholar]
  24. Holland, S., Lodwig, E., Sideri, T., Reader, T., Clarke, I., Gkargkas, K., … Avery, S. V. (2007). Application of the comprehensive set of heterozygous yeast deletion mutants to elucidate the molecular basis of cellular chromium toxicity. Genome Biology, 8(12), R268. [Google Scholar]
  25. Hosiner, D., Lempiäinen, H., Reiter, W., Urban, J., Loewith, R., Ammerer, G., … Schüller, C. (2009). Arsenic toxicity to Saccharomyces cerevisiae is a consequence of inhibition of the TORC1 kinase combined with a chronic stress response. Molecular Biology of the Cell, 20(3), 1048–1057. [Google Scholar]
  26. Jacobson, T., Navarrete, C., Sharma, S. K., Sideri, T. C., Ibstedt, S., Priya, S., … Tamás, M. J. (2012). Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast. J Cell Sci, jcs-107029. [Google Scholar]
  27. Kim, K.-W., Chanpiwat, P., Hanh, H. T., Phan, K., & Sthiannopkao, S. (2011). Arsenic geochemistry of groundwater in Southeast Asia. Frontiers of Medicine, 5(4), 420–433. [Google Scholar] [Crossref] 
  28. Kiriyama, K., Hara, K. Y., & Kondo, A. (2012). Extracellular glutathione fermentation using engineered Saccharomyces cerevisiae expressing a novel glutathione exporter. Applied Microbiology and Biotechnology, 96(4), 1021–1027. [Google Scholar]
  29. Kitchin, K. T., & Wallace, K. (2008). The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. Journal of Inorganic Biochemistry, 102(3), 532–539. [Google Scholar]
  30. Kuge, S., & Jones, N. (1994). YAP1 dependent activation of TRX2 is essential for the response of Saccharomyces cerevisiae to oxidative stress by hydroperoxides. The EMBO Journal, 13(3), 655–664. [Google Scholar]
  31. Kumar, N. V., Yang, J., Pillai, J. K., Rawat, S., Solano, C., Kumar, A., … Tamás, M. J. (2016). Arsenic directly binds to and activates the yeast AP-1-like transcription factor Yap8. Molecular and Cellular Biology, 36(6), 913–922. [Google Scholar]
  32. Lee, J., Godon, C., Lagniel, G., Spector, D., Garin, J., Labarre, J., & Toledano, M. B. (1999). Yap1 and Skn7 control two specialized oxidative stress response regulons in yeast. Journal of Biological Chemistry, 274(23), 16040–16046. [Google Scholar]
  33. Lee, J., & Levin, D. E. (2015). Rgc2 Regulator of Glycerol Channel Fps1 Functions as Homo-and Hetero-dimers with Rgc1. Eukaryotic Cell, EC-00073. [Google Scholar]
  34. Lee, J., & Levin, D. E. (2018). Intracellular mechanism by which arsenite activates the yeast stress MAPK Hog1. Molecular Biology of the Cell, 29(15), 1904–1915. [Google Scholar]
  35. Lemire, J. A., Harrison, J. J., & Turner, R. J. (2013). Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nature Reviews. Microbiology, 11(6), 371–384. [Google Scholar] [Crossref] 
  36. Liu, Z., Boles, E., & Rosen, B. P. (2004). Arsenic trioxide uptake by hexose permeases in Saccharomyces cerevisiae. Journal of Biological Chemistry, 279(17), 17312–17318. [Google Scholar]
  37. Liu, Z., Sanchez, M. A., Jiang, X., Boles, E., Landfear, S. M., & Rosen, B. P. (2006). Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid. Biochemical and Biophysical Research Communications, 351(2), 424–430. [Google Scholar]
  38. Maciaszczyk-Dziubinska, E., Wawrzycka, D., & Wysocki, R. (2012). Arsenic and antimony transporters in eukaryotes. International Journal of Molecular Sciences, 13(3), 3527–3548. [Google Scholar]
  39. Matia‐González, A. M., & Rodríguez‐Gabriel, M. A. (2011). Slt2 MAPK pathway is essential for cell integrity in the presence of arsenate. Yeast, 28(1), 9–17. [Google Scholar]
  40. Menezes, R. A., Pimentel, C., Silva, A. R. C., Amaral, C., Merhej, J., Devaux, F., & Rodrigues-Pousada, C. (2017). Mediator, SWI/SNF and SAGA complexes regulate Yap8-dependent transcriptional activation of ACR2 in response to arsenate. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 1860(4), 472–481. [Google Scholar]
  41. Migdal, I., Ilina, Y., Tamás, M. J., & Wysocki, R. (2008). Mitogen-activated protein kinase Hog1 mediates adaptation to G1 checkpoint arrest during arsenite and hyperosmotic stress. Eukaryotic Cell, 7(8), 1309–1317. [Google Scholar]
  42. Morgan, B. A., Banks, G. R., Toone, W. M., Raitt, D., Kuge, S., & Johnston, L. H. (1997). The Skn7 response regulator controls gene expression in the oxidative stress response of the budding yeast Saccharomyces cerevisiae. The EMBO Journal, 16(5), 1035–1044. [Google Scholar]
  43. Mukhopadhyay, R., & Rosen, B. P. (1998). Saccharomyces cerevisiae ACR2 gene encodes an arsenate reductase. FEMS Microbiology Letters, 168(1), 127–136. [Google Scholar]
  44. Mukhopadhyay, R., Shi, J., & Rosen, B. P. (2000). Purification and Characterization of Acr2p, the Saccharomyces cerevisiae Arsenate Reductase. Journal of Biological Chemistry, 275(28), 21149–21157. [Google Scholar]
  45. Nathaniel, M. M. (2005). Arsenic: In Search of an Antidote to a Global Poison. Environmental Health Perspectives, 113(6), A378–A386. [Google Scholar] [Crossref] 
  46. Outten, C. E., & Albetel, A.-N. (2013). Iron sensing and regulation in Saccharomyces cerevisiae: ironing out the mechanistic details. Current Opinion in Microbiology, 16(6), 662–668. [Google Scholar]
  47. Porquet, A., & Filella, M. (2007). Structural evidence of the similarity of Sb (OH) 3 and As (OH) 3 with glycerol: implications for their uptake. Chemical Research in Toxicology, 20(9), 1269–1276. [Google Scholar]
  48. Ralph, S. J. (2008). Arsenic-based antineoplastic drugs and their mechanisms of action. Metal-Based Drugs, 2008. [Google Scholar]
  49. Ramírez-Solís, A., Mukopadhyay, R., Rosen, B. P., & Stemmler, T. L. (2004). Experimental and Theoretical Characterization of Arsenite in Water: Insights into the Coordination Environment of As− O. Inorganic Chemistry, 43(9), 2954–2959. [Google Scholar]
  50. Rathod, J., Tu, H.-P., Chang, Y.-I., Chu, Y.-H., Tseng, Y.-Y., Jean, J.-S., & Wu, W.-S. (2018). YARG: A repository for arsenic-related genes in yeast. PloS One, 13(7), e0201204. [Google Scholar]
  51. Smith, A. H., Hopenhayn-Rich, C., Bates, M. N., Goeden, H. M., Hertz-Picciotto, I., Duggan, H. M., … Smith, M. T. (1992). Cancer risks from arsenic in drinking water. Environmental Health Perspectives, 97, 259–267. [Google Scholar] [Crossref] 
  52. Sorin, A., Rosas, G., & Rao, R. (1997). PMR1, a Ca2+-ATPase in yeast Golgi, has properties distinct from sarco/endoplasmic reticulum and plasma membrane calcium pumps. Journal of Biological Chemistry, 272(15), 9895–9901. [Google Scholar]
  53. Tamás, M. J., Fauvet, B., Christen, P., & Goloubinoff, P. (2018). Misfolding and aggregation of nascent proteins: a novel mode of toxic cadmium action in vivo. Current Genetics, 64(1), 177–181. [Google Scholar]
  54. Tamás, M. J., Sharma, S. K., Ibstedt, S., Jacobson, T., & Christen, P. (2014). Heavy metals and metalloids as a cause for protein misfolding and aggregation. Biomolecules, 4(1), 252–267. [Google Scholar]
  55. Thorsen, M., Lagniel, G., Kristiansson, E., Junot, C., Nerman, O., Labarre, J., & Tamás, M. J. (2007). Quantitative transcriptome, proteome, and sulfur metabolite profiling of the Saccharomyces cerevisiae response to arsenite. Physiological Genomics, 30(1), 35–43. [Google Scholar]
  56. Thorsen, M., Perrone, G. G., Kristiansson, E., Traini, M., Ye, T., Dawes, I. W., … Tamás, M. J. (2009). Genetic basis of arsenite and cadmium tolerance in Saccharomyces cerevisiae. BMC Genomics, 10(1), 105. [Google Scholar]
  57. Vahter, M. (2008). Health effects of early life exposure to arsenic. Basic & Clinical Pharmacology & Toxicology, 102(2), 204–211. [Google Scholar] [Crossref] 
  58. Vujcic, M., Shroff, M., & Singh, K. K. (2007). Genetic determinants of mitochondrial response to arsenic in yeast Saccharomyces cerevisiae. Cancer Research, 67(20), 9740–9749. [Google Scholar]
  59. Wysocki, R., Bobrowicz, P., & Ułaszewski, S. (1997). The Saccharomyces cerevisiae ACR3 gene encodes a putative membrane protein involved in arsenite transport. Journal of Biological Chemistry, 272(48), 30061–30066. [Google Scholar]
  60. Wysocki, R., & Tamás, M. J. (2011). Saccharomyces cerevisiae as a model organism for elucidating arsenic tolerance mechanisms. In Cellular Effects of Heavy Metals (pp. 87–112). Springer. [Google Scholar]
  61. Yang, X., Lau, K.-Y., Sevim, V., & Tang, C. (2013). Design principles of the yeast G1/S switch. PLoS Biology, 11(10), e1001673. [Google Scholar]
  62. Yompakdee, C., Bun-ya, M., Shikata, K., Ogawa, N., Harashima, S., & Oshima, Y. (1996). A putative new membrane protein, Pho86p, in the inorganic phosphate uptake system of Saccharomyces cerevisiae. Gene, 171(1), 41–47. [Google Scholar]
  63. Yu, M.-H., & Tsunoda, H. (2004). Environmental toxicology: biological and health effects of pollutants. crc press. [Google Scholar]