Skip to main content

Advertisement

Springer Nature Link
Log in

Molecular Biology of Cadmium Toxicity in Saccharomyces cerevisiae

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Cadmium (Cd) is a toxic heavy metal mainly originating from industrial activities and causes environmental pollution. To better understand its toxicity and pollution remediation, we must understand the effects of Cd on living beings. Saccharomyces cerevisiae (budding yeast) is an eukaryotic unicellular model organism. It has provided much scientific knowledge about cellular and molecular biology in addition to its economic benefits. Effects associated with copper and zinc, sulfur and selenium metabolism, calcium (Ca2+) balance/signaling, and structure of phospholipids as a result of exposure to cadmium have been evaluated. In yeast as a result of cadmium stress, “mitogen-activated protein kinase,” “high osmolarity glycerol,” and “cell wall integrity” pathways have been reported to activate different signaling pathways. In addition, abnormalities and changes in protein structure, ribosomes, cell cycle disruption, and reactive oxygen species (ROS) following cadmium cytotoxicity have also been detailed. Moreover, the key OLE1 gene that encodes for delta-9 FA desaturase in relation to cadmium toxicity has been discussed in more detail. Keeping all these studies in mind, an attempt has been made to evaluate published cellular and molecular toxicity data related to Cd stress, and specifically published on S. cerevisiae.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ashraf MY, Roohi M, Iqbal Z, Ashraf M, Ozturk M, Gucel S (2015) Cadmium (Cd) and lead (Pb) induced inhibition in growth and alteration in some biochemical attributes and mineral accumulation in mung bean [Vigna radiata (L.) Wilczek]. Commun Soil Sci Plant Anal 47:405–413

    Google Scholar 

  2. Genchi G, Sinicropi MS, Lauria G, Carocci A, Catalano A (2020) The effects of cadmium toxicity. Int J Environ Res Public Health 17(11):3782

    Article  CAS  PubMed Central  Google Scholar 

  3. Farooq M, Ullah A, Usman M, Siddique KH (2020) Application of zinc and biochar help to mitigate cadmium stress in bread wheat raised from seeds with high intrinsic zinc. Chemosphere 260:127652

    Article  CAS  PubMed  Google Scholar 

  4. El-Esawi MA, Elkelish A, Soliman M, Elansary HO, Zaid A, Wani SH (2020) Serratia marcescens BM1 enhances cadmium stress tolerance and phytoremediation potential of soybean through modulation of osmolytes, leaf gas exchange, antioxidant machinery, and stress-responsive genes expression. Antioxidants 9(1):43

    Article  CAS  PubMed Central  Google Scholar 

  5. Ghori NH, Ghori T, Hayat MQ, Imadi SR, Gul A, Altay V, Ozturk M (2019) Heavy metal stress and responses in plants. Int J Environ Sci Technol 16(3):1807–1828

    Article  CAS  Google Scholar 

  6. Bertin G, Averbeck D (2006) Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie 88:1549–1559

    Article  CAS  PubMed  Google Scholar 

  7. Chunhabundit R (2016) Cadmium exposure and potential health risk from foods in contaminated area, Thailand. Toxicological Research 32:65–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhang H, Reynolds M (2019) Cadmium exposure in living organisms: a short review. Sci Total Environ 678:761–767

    Article  CAS  PubMed  Google Scholar 

  9. Goering PL, Waalkes MP, Klaassen CD (1994) Toxicology of metals, biochemical effects. Handbook of experimental pharmacology: toxicology of metals. Biochemical Effects. Springer, N Y 115:189–214

    Google Scholar 

  10. Hengstler JG, Bolm-Audorff U, Faldum A, Janssen K, Reifenrath M, Götte W, Gebhard S (2003) Occupational exposure to heavy metals: DNA damage induction and DNA repair inhibition prove co-exposures to cadmium, cobalt and lead as more dangerous than hitherto expected. Carcinogenesis 24:63–73

    Article  CAS  PubMed  Google Scholar 

  11. Zalups RK, Ahmad S (2003) Molecular handling of cadmium in transporting epithelia. Toxicol Appl Pharmacol 186:163–188

    Article  CAS  PubMed  Google Scholar 

  12. Bishak YK, Payahoo L, Osatdrahimi A, Nourazarian A (2015) Mechanisms of cadmium carcinogenicity in the gastrointestinal tract. Asian Pacific Journal Cancer Prevention 16:9–21

    Article  Google Scholar 

  13. Larsson SC, Orsini N, Wolk A (2015) Urinary cadmium concentration and risk of breast cancer: a systematic review and dose-response meta-analysis. Am J Epidemiol 182:375–380

    Article  PubMed  Google Scholar 

  14. Inglot P, Lewinska A, Potocki L, Oklejewicz B, Tabecka-Lonczynska A, Koziorowski M, Wnuk M (2012) Cadmium-induced changes in genomic DNA-methylation status increase aneuploidy events in a pig Robertsonian translocation model. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 747:182–189

    Article  CAS  Google Scholar 

  15. Xiao CL, Liu Y, Tu W, Xia YJ, Tian KM, Zhou X (2016) Research progress of the mechanisms underlying cadmium-induced carcinogenesis. Chinese Journal of Preventive Medicine 50:380–384

    CAS  PubMed  Google Scholar 

  16. McMurray CT, Tainer JA (2003) Cancer, cadmium and genome integrity. Nat Genet 34:239–241

    Article  CAS  PubMed  Google Scholar 

  17. Stohs SJ, Bagchi D (1995) Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 18:321–336

    Article  CAS  PubMed  Google Scholar 

  18. Knight AS, Zhou EY, Francis MB (2015) Development of peptoid-based ligands for the removal of cadmium from biological media. Chem Sci 6:4042–4048

    Article  CAS  PubMed Central  Google Scholar 

  19. Li X, Jiang X, Sun J, Zhu C, Li X, Tian L, Bai W (2017) Cytoprotective effects of dietary flavonoids against cadmium-induced toxicity. Ann N Y Acad Sci 1398:5–19

    Article  CAS  PubMed  Google Scholar 

  20. Bánfalvi G (2011) Cellular effects of heavy metals. Springer

  21. Tamás MJ, Labarre J, Toledano MB, Wysocki R (2006) Mechanisms of toxic metal tolerance in yeast BT. In: Tamas MJ, Martinoia E (eds) Molecular biology of metal homeostasis and detoxification: from microbes to man. Springer, Berlin, Heidelberg, pp 395–454

    Chapter  Google Scholar 

  22. Huang X, Li Y, Pan J, Li M, Lai Y, Gao J, Li X (2016) RNA-Seq identifies redox balance related gene expression alterations under acute cadmium exposure in yeast. Environ Microbiol Rep 8:1038–1047

    Article  CAS  PubMed  Google Scholar 

  23. Li ZS, Lu YP, Zhen RG, Szczypka M, Thiele DJ, Rea PA (1997) A new pathway for vacuolar cadmium sequestration in Saccharomyces cerevisiae: YCF1-catalyzed transport of bis(glutathionato)cadmium. Proc Natl Acad Sci U S A 94:42–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Szczypka MS, Wemmie JA, Moye-Rowley WS, Thiele DJ (1994) A yeast metal resistance protein similar to human cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance- associated protein. J Biol Chem 269:22853–22857

    Article  CAS  PubMed  Google Scholar 

  25. Ghosh M, Shen J, Rosen BP (1999) Pathways of As (III) detoxification in Saccharomyces cerevisiae. Proc Natl Acad Sci 96:5001–5006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gueldry O, Lazard M, Delort F, Dauplais M, Grigoras I, Blanquet S, Plateau P (2003) Ycf1p-dependent Hg(II) detoxification in Saccharomyces cerevisiae. Eur J Biochem 270:2486–2496

    Article  CAS  PubMed  Google Scholar 

  27. Lazard M, Ha-Duong NT, Mounié S, Perrin R, Plateau P, Blanquet S (2011) Selenodiglutathione uptake by the Saccharomyces cerevisiae vacuolar ATP-binding cassette transporter Ycf1p. FEBS J 278(21):4112–4121

    Article  CAS  PubMed  Google Scholar 

  28. Guerinot ML (2000) The ZIP family of metal transporters. Biochimica et Biophysica Acta (BBA)-Biomembranes 1465(1–2):190–198

    Article  CAS  Google Scholar 

  29. Lazard M, Blanquet S, Fisicaro P, Labarraque G, Plateau P (2010) Uptake of selenite by Saccharomyces cerevisiae involves the high and low affinity orthophosphate transporters. J Biol Chem 285(42):32029–32037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gomes DS, Fragoso LC, Riger CJ, Panek AD, Eleutherio ECA (2002) Regulation of cadmium uptake by Saccharomyces cerevisiae. Biochimica et Biophysica Acta (BBA)-General Subjects 1573(1):21–25

    Article  CAS  Google Scholar 

  31. Adle DJ, Lee J (2008) Expressional control of a cadmium-transporting P1B-type ATPase by a metal sensing degradation signal. J Biol Chem 283:31460–31468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Adle DJ, Wei W, Smith N, Bies JJ, Lee J (2009) Cadmium-mediated rescue from ER-associated degradation induces expression of its exporter. Proc Natl Acad Sci 106:10189–10194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Adle DJ, Sinani D, Kim H, Lee J (2007) A cadmium-transporting P1B-type ATPase in yeast Saccharomyces cerevisiae. J Biol Chem 282:947–955

    Article  CAS  PubMed  Google Scholar 

  34. Smith N, Wei W, Zhao M, Qin X, Seravalli J, Kim H, Lee J (2016) Cadmium and secondary structure-dependent function of a degron in Pca1p cadmium exporter. Journal of Biological Chemistry jbc-M116

  35. Wysocki R, Tamás MJ (2010) How Saccharomyces cerevisiae copes with toxic metals and metalloids. FEMS Microbiol Rev 34:925–951

    Article  CAS  PubMed  Google Scholar 

  36. Robinson NJ, Winge DR (2010) Copper metallochaperones. Annu Rev Biochem 79:537–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Culotta VC, Yang M, O’Halloran TV (2006) Activation of superoxide dismutases: putting the metal to the pedal. Biochimica et Biophysica Acta (BBA)-Molecular Cell Res 1763:747–758

    Article  CAS  Google Scholar 

  38. Pufahl RA, Singer CP, Peariso KL, Lin SJ, Schmidt PJ, Fahrni CJ, Culotta VC, Penner-Hahn JE, O’halloran TV (1997) Metal ion chaperone function of the soluble Cu (I) receptor Atx1. Science 278:853–856

    Article  CAS  PubMed  Google Scholar 

  39. Huffman DL, O’Halloran TV (2001) Function, structure, and mechanism of intracellular copper trafficking proteins. Annu Rev Biochem 70:677–701

    Article  CAS  PubMed  Google Scholar 

  40. Heo DH, Baek IJ, Kang HJ, Kim JH, Chang M, Kang CM, Yun CW (2012) Cd2+ binds to Atx1 and affects the physical interaction between Atx1 and Ccc2 in Saccharomyces cerevisiae. Biotechnol Lett 34:303–307

    Article  CAS  PubMed  Google Scholar 

  41. Wei W, Smith N, Wu X, Kim H, Seravalli J, Khalimonchuk O, Lee J (2014) YCF1-mediated cadmium resistance in yeast is dependent on copper metabolism and antioxidant enzymes. Antioxid Redox Signal 21:1475–1489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fauchon M, Lagniel G, Aude JC, Lombardia L, Soularue P, Petat C, Labarre J (2002) Sulfur sparing in the yeast proteome in response to sulfur demand. Mol Cell 9:713–723

    Article  CAS  PubMed  Google Scholar 

  43. Vido K, Spector D, Lagniel G, Lopez S, Toledano MB, Labarre J (2001) A proteome analysis of the cadmium response in Saccharomyces cerevisiae. J Biol Chem 276:8469–8474

    Article  CAS  PubMed  Google Scholar 

  44. Jamieson D (2002) Saving sulfur. Nat Genet 31:228–230

    Article  CAS  PubMed  Google Scholar 

  45. Thomas D, Surdin-Kerjan Y (1997) Metabolism of sulfur amino acids in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 61:503–532

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Flick K, Ouni I, Wohlschlegel JA, Capati C, McDonald WH, Yates JR, Kaiser P (2004) Proteolysis-independent regulation of the transcription factor Met4 by a single Lys 48-linked ubiquitin chain. Nat Cell Biol 6:634–641

    Article  CAS  PubMed  Google Scholar 

  47. Kaiser P, Flick K, Wittenberg C, Reed SI (2000) Regulation of transcription by ubiquitination without proteolysis. Cell 102:303–314

    Article  CAS  PubMed  Google Scholar 

  48. Rouillon A, Barbey R, Patton EE, Tyers M, Thomas D (2000) Feedback-regulated degradation of the transcriptional activator Met4 is triggered by the SCF(Met30) complex. EMBO J 19:282–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Flick K, Raasi S, Zhang H, Yen JL, Kaiser P (2006) A ubiquitin-interacting motif protects polyubiquitinated Met4 from degradation by the 26S proteasome. Nat Cell Biol 8:509–515

    Article  CAS  PubMed  Google Scholar 

  50. Kaiser P, Su N-Y, Yen JL, Ouni I, Flick K (2006) The yeast ubiquitin ligase SCFMet30: connecting environmental and intracellular conditions to cell division. Cell Div 1:16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Patton EE, Peyraud C, Rouillon A, Surdin-Kerjan Y, Tyers M, Thomas D (2000) SCF(Met30)-mediated control of the transcriptional activator Met4 is required for the G(1)-S transition. EMBO J 19:1613–1624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Su NY, Flick K, Kaiser P (2005) The F-Box protein Met30 is required for multiple steps in the budding yeast cell cycle. Mol Cell Biol 25:3875–3885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Barbey R, Baudouin-Cornu P, Lee TA, Rouillon A, Zarzov P, Tyers M, Thomas D (2005) Inducible dissociation of SCF & lt; sup & gt; Met30</sup> ubiquitin ligase mediates a rapid transcriptional response to cadmium. EMBO J 24:521–532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yen JL, Su NY, Kaiser P (2005) The yeast ubiquitin ligase SCFMet30 regulates heavy metal response. Mol Biol Cell 16:1872–1882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Flick K, Kaiser P (2011) Cellular mechanisms to respond to cadmium exposure: ubiquitin ligases. In: Banfalvi G (ed) Cellular effects of heavy metals. Springer, Berlin, pp 275–289

    Chapter  Google Scholar 

  56. Zwolak I (2019) The role of selenium in arsenic and cadmium toxicity: an updated review of scientific literature. Biol Trace Elem Res 193:44–63. https://doi.org/10.1007/s12011-019-01691-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kieliszek M, Błażejak S, Bzducha-Wróbel A, Kurcz A (2016) Effects of selenium on morphological changes in Candida utilis ATCC 9950 yeast cells. Biol Trace Elem Res 169:387–393

    Article  CAS  PubMed  Google Scholar 

  58. Dauplais M, Lazard M, Blanquet S, Plateau P (2013) Neutralization by metal ions of the toxicity of sodium selenide. PLoS One 8(1):e54353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kieliszek M, Błażejak S, Bzducha-Wróbel A, Kot AM (2019) Effect of selenium on lipid and amino acid metabolism in yeast cells. Biol Trace Elem Res 187:316–327

    Article  CAS  PubMed  Google Scholar 

  60. Kieliszek M, Błażejak S, Bzducha-Wróbel A, Kot AM (2019) Effect of selenium on growth and antioxidative system of yeast cells. Mol Biol Rep 46:1797–1808

    Article  CAS  PubMed  Google Scholar 

  61. Ismael MA, Elyamine AM, Moussa MG, Cai M, Zhao X, Hu C (2019) Cadmium in plants: uptake, toxicity, and its interactions with selenium fertilizers. Metallomics 11:255–277. https://doi.org/10.1039/c8mt00247a

    Article  CAS  PubMed  Google Scholar 

  62. Pardo B, Crabbé L, Pasero P (2017) Signaling pathways of replication stress in yeast. FEMS Yeast Research 17(2):fow101

  63. Chen S, Smolka MB, Zhou H (2007) Mechanism of Dun1 activation by Rad53 phosphorylation in Saccharomyces cerevisiae. J Biol Chem 282:986–995

    Article  CAS  PubMed  Google Scholar 

  64. Elledge SJ, Zhou Z, Allen JB, Navas TA (1993) DNA damage and cell cycle regulation of ribonucleotide reductase. Bioessays 15:333–339

    Article  CAS  PubMed  Google Scholar 

  65. Chabes A, Domkin V, Thelander L (1999) Yeast Sml1, a protein inhibitor of ribonucleotide reductase. J Biol Chem 274:36679–36683

    Article  CAS  PubMed  Google Scholar 

  66. Zhao X, Rothstein R (2002) The Dun1 checkpoint kinase phosphorylates and regulates the ribonucleotide reductase inhibitor Sml1. Proc Natl Acad Sci 99:3746–3751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Chabes A, Georgieva B, Domkin V, Zhao X, Rothstein R, Thelander L (2003) Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribonucleotide reductase. Cell 112:391–401

    Article  CAS  PubMed  Google Scholar 

  68. Håkansson P, Hofer A, Thelander L (2006) Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage and in resting cells. J Biol Chem 281:7834–7841

    Article  PubMed  CAS  Google Scholar 

  69. Andreson BL, Gupta A, Georgieva BP, Rothstein R (2010) The ribonucleotide reductase inhibitor, Sml1, is sequentially phosphorylated, ubiquitylated and degraded in response to DNA damage. Nucleic Acids Res 38:6490–6501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Huang M, Zhou Z, Elledge SJ (1998) The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor. Cell 94:595–605

    Article  CAS  PubMed  Google Scholar 

  71. Domki V, Thelander L, Chabes A (2002) Yeast DNA damage-inducible Rnr3 has a very low catalytic activity strongly stimulated after the formation of a cross-talking Rnr1/Rnr3 complex. J Biol Chem 277:18574–18578

    Article  CAS  Google Scholar 

  72. Baek IJ, Kang HJ, Chang M, Choi ID, Kang CM, Yun CW (2012) Cadmium inhibits the protein degradation of Sml1 by inhibiting the phosphorylation of Sml1 in Saccharomyces cerevisiae. Biochem Biophys Res Commun 424:385–390

    Article  CAS  PubMed  Google Scholar 

  73. Muthukumar K, Nachiappan V (2010) Cadmium-induced oxidative stress in Saccharomyces cerevisiae. Indian J Biochem Biophys 47(6):383–387

    CAS  PubMed  Google Scholar 

  74. Cuypers A, Plusquin M, Remans T, Jozefczak M, Keunen E, Gielen H, Smeets K (2010) Cadmium stress: an oxidative challenge. BioMetals 23:927–940

    Article  CAS  PubMed  Google Scholar 

  75. Nair AR, DeGheselle O, Smeets K, Van Kerkhove E, Cuypers A (2013) Cadmium-induced pathologies: where is the oxidative balance lost (or not)? International Journal of Molecular Sciences:6116–6143

  76. Valko MMHCM, Morris H, Cronin MTD (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–1208

    Article  CAS  PubMed  Google Scholar 

  77. Choong G, Liu Y, Templeton DM (2014) Interplay of calcium and cadmium in mediating cadmium toxicity. Chem Biol Interact 211:54–65

    Article  CAS  PubMed  Google Scholar 

  78. Wang X, Yi M, Liu H, Han Y, Yi H (2016) Reactive oxygen species and Ca2+ are involved in cadmium-induced cell killing in yeast cells. Can J Microbiol 63:153–159

    Article  PubMed  CAS  Google Scholar 

  79. Wu L, Chen Y, Gao H, Yin J, Huang L (2016) Cadmium-induced cell killing in Saccharomyces cerevisiae involves increases in intracellular NO levels. FEMS Microbiology Letters 363(6):fnw032

    Article  PubMed  CAS  Google Scholar 

  80. Cyert MS, Philpott CC (2013) Regulation of cation balance in Saccharomyces cerevisiae. Genetics 193:677–713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ruta LL, Popa VC, Nicolau I, Danet AF, Iordache V, Neagoe AD, Farcasanu IC (2014) Calcium signaling mediates the response to cadmium toxicity in Saccharomyces cerevisiae cells. FEBS Lett 588:3202–3212

    Article  CAS  PubMed  Google Scholar 

  82. Batiza AF, Schulz T, Masson PH (1996) Yeast respond to hypotonic shock with a calcium pulse. J Biol Chem 271:23457–23462

    Article  Google Scholar 

  83. Matsumoto TK, Ellsmore AJ, Cessna SG, Low PS, Pardo JM, Bressan RA, Hasegawa PM (2002) An osmotically induced cytosolic Ca2+ transient activates calcineurin signaling to mediate ion homeostasis and salt tolerance of Saccharomyces cerevisiae. J Biol Chem 277:33075–33080

    Article  CAS  PubMed  Google Scholar 

  84. Kanzaki M, Nagasawa M, Kojima I, Sato C, Naruse K, Sokabe M, Iida H (1999) Molecular identification of a eukaryotic, stretch-activated nonselective cation channel. Science 285:882–886

    Article  CAS  PubMed  Google Scholar 

  85. Viladevall L, Serrano R, Ruiz A, Domenech G, Giraldo J, Barceló A, Ariño J (2004) Characterization of the calcium-mediated response to alkaline stress in Saccharomyces cerevisiae. J Biol Chem 279:43614–43624

    Article  CAS  PubMed  Google Scholar 

  86. Catterall WA (2000) Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 16:521–555

    Article  CAS  PubMed  Google Scholar 

  87. Popa CV, Dumitru I, Ruta LL, Danet AF, Farcasanu IC (2010) Exogenous oxidative stress induces Ca2+ release in the yeast Saccharomyces cerevisiae. FEBS J 277:4027–4038

    Article  CAS  PubMed  Google Scholar 

  88. Cunningham KW, Fink GR (1994a) Ca2+ transport in Saccharomyces cerevisiae. J Exp Biol 196:157–166

    Article  CAS  PubMed  Google Scholar 

  89. Cunningham KW, Fink GR (1994b) Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking PMC1, a homolog of plasma membrane Ca2+ ATPases. J Cell Biol 124:351–363

    Article  CAS  PubMed  Google Scholar 

  90. Cunningham KW, Fink GR (1996) Calcineurin inhibits VCX1-dependent H+/Ca2+ exchange and induces Ca2+ ATPases in Saccharomyces cerevisiae. Mol Cell Biol 16:2226–2237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Miseta A, Kellermayer R, Aiello DP, Fu L, Bedwell DM (1999) The vacuolar Ca2+/H+ exchanger Vcx1p/Hum1p tightly controls cytosolic Ca2+ levels in S. cerevisiae. FEBS Lett 451(2):132–136

    Article  CAS  PubMed  Google Scholar 

  92. 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. J Biol Chem 272:9895–9901

    Article  CAS  PubMed  Google Scholar 

  93. Strayle J, Pozzan T, Rudolph HK (1999) Steady-state free Ca2+ in the yeast endoplasmic reticulum reaches only 10 μM and is mainly controlled by the secretory pathway pump Pmr1. The EMBO Journal 18:4733LP

    Article  Google Scholar 

  94. Matheos DP, Kingsbury TJ, Ahsan US, Cunningham KW (1997) Tcn1p/Crz1p, a calcineurin-dependent transcription factor that differentially regulates gene expression in Saccharomyces cerevisiae. Genes Dev 11:3445–3458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Stathopoulos AM, Cyert MS (1997) Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast. Genes Dev 11:3432–3444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Locke EG, Bonilla M, Liang L, Takita Y, Cunningham KW (2000) A homolog of voltage-gated Ca(2+) channels stimulated by depletion of secretory Ca(2+) in yeast. Mol Cell Biol 20:6686–6694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Palmer CP, Zhou XL, Lin J, Loukin SH, Kung C, Saimi Y (2001) A TRP homolog in Saccharomyces cerevisiae forms an intracellular Ca2+-permeable channel in the yeast vacuolar membrane. Proc Natl Acad Sci 98:7801–7805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Su Z, Zhou X, Loukin SH, Haynes WJ, Saimi Y, Kung C (2009) The use of yeast to understand TRP-channel mechanosensitivity. Pflügers Archiv-European Journal of Physiology 458(5):861–867

    Article  CAS  PubMed  Google Scholar 

  99. Rajakumar S, Bhanupriya N, Ravi C, Nachiappan V (2016) Endoplasmic reticulum stress and calcium imbalance are involved in cadmium-induced lipid aberrancy in Saccharomyces cerevisiae. Cell Stress and Chaperones 21(5):895–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Rajakumar S, Ravi C, Nachiappan V (2016) Defect of zinc transporter ZRT1 ameliorates cadmium induced lipid accumulation in Saccharomyces cerevisiae. Metallomics 8:453–460

    Article  CAS  PubMed  Google Scholar 

  101. Muthukumar K, Nachiappan V (2013) Phosphatidylethanolamine from phosphatidylserine decarboxylase2 is essential for autophagy under cadmium stress in Saccharomyces cerevisiae. Cell Biochem Biophys 67:1353–1363

    Article  CAS  PubMed  Google Scholar 

  102. Jonikas MC, Collins SR, Denic V, Oh E, Quan EM, Schmid V, Weissman JS (2009) Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum. Science 323:1693–1697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Thibault G, Shui G, Kim W, McAlister GC, Ismail N, Gygi SP, Ng DTW (2012) The membrane stress response buffers lethal effects of lipid disequilibrium by reprogramming the protein homeostasis network. Mol Cell 48:16–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Martin CE, Oh C-S, Jiang Y (2007) Regulation of long chain unsaturated fatty acid synthesis in yeast. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 1771:271–285

    CAS  Google Scholar 

  105. Stukey JE, McDonough VM, Martin CE (1989) Isolation and characterization of OLE1, a gene affecting fatty acid desaturation from Saccharomyces cerevisiae. J Biol Chem 264:16537–16544

    Article  CAS  PubMed  Google Scholar 

  106. Siso MIG, Becerra M, Maceiras ML, Vázquez ÁV, Cerdán ME (2012) The yeast hypoxic responses, resources for new biotechnological opportunities. Biotechnol Lett 34:2161–2173

    Article  CAS  Google Scholar 

  107. Rajakumar S, Abhishek A, Selvam GS, Nachiappan V (2020) Effect of cadmium on essential metals and their impact on lipid metabolism in Saccharomyces cerevisiae. Cell Stress and Chaperones 25:19–33

    Article  CAS  PubMed  Google Scholar 

  108. Kaya C, Ashraf M, Alyemeni MN, Ahmad P (2020) Responses of nitric oxide and hydrogen sulfide in regulating oxidative defence system in wheat plants grown under cadmium stress. Physiol Plant 168(2):345–360

    CAS  PubMed  Google Scholar 

  109. Rajakumar S, Nachiappan V (2017) Lipid droplets alleviate cadmium induced cytotoxicity in Saccharomyces cerevisiae. Toxicology Research 6:30–41

    Article  CAS  PubMed  Google Scholar 

  110. Fang Z, Chen Z, Wang S, Shi P, Shen Y, Zhang Y, Huang Z (2017) Overexpression of OLE1 enhances cytoplasmic membrane stability and confers resistance to cadmium in Saccharomyces cerevisiae. Applied Environmental Microbiology 83:e02319–e02316

    Article  CAS  PubMed  Google Scholar 

  111. Huang Z, Yu Y, Fang Z, Deng Y, Shen Y, Shi P (2018) OLE1 reduces cadmium-induced oxidative damage in Saccharomyces cerevisiae. FEMS Microbiology Letters 365:fny193

  112. Thompson JE, Froese CD, Madey E, Smith MD, Hong Y (1998) Lipid metabolism during plant senescence. Prog Lipid Res 37:119–141

    Article  CAS  PubMed  Google Scholar 

  113. Tsaluchidu S, Puri BK (2008) Fatty acids and oxidative stress. Ann General Psychiatry 7(Suppl 1):S86

    Article  Google Scholar 

  114. Kwast KE, Burke PV, Staahl BT, Poyton RO (1999) Oxygen sensing in yeast: evidence for the involvement of the respiratory chain in regulating the transcription of a subset of hypoxic genes. Proc Natl Acad Sci 96(10):5446–5451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Muthukumar K, Rajakumar S, Sarkar MN, Nachiappan V (2011) Glutathione peroxidase3 of Saccharomyces cerevisiae protects phospholipids during cadmium-induced oxidative stress. Antonie Van Leeuwenhoek 99:761–771

    Article  CAS  PubMed  Google Scholar 

  116. Kudo N, Nakagawa Y, Waku K, Kawashima Y, Kozuka H (1991) Prevention by zinc of cadmium inhibition of stearoyl-CoA desaturase in rat liver. Toxicology 68:133–142

    Article  CAS  PubMed  Google Scholar 

  117. Shivapurkar N, Reddy J, Chaudhary PM, Gazdar AF (2003) Apoptosis and lung cancer: a review. J Cell Biochem 88:885–898

    Article  CAS  PubMed  Google Scholar 

  118. Rodríguez-Peña JM, García R, Nombela C, Arroyo J (2010) The high-osmolarity glycerol (HOG) and cell wall integrity (CWI) signalling pathways interplay: a yeast dialogue between MAPK routes. Yeast 27:495–502

    Article  PubMed  CAS  Google Scholar 

  119. Jiang L, Cao C, Zhang L, Lin W, Xia J, Xu H, Zhang Y (2014) Cadmium-induced activation of high osmolarity glycerol pathway through its Sln1 branch is dependent on the MAP kinase kinase kinase Ssk2, but not its paralog Ssk22, in budding yeast. FEMS Yeast Res 14(8):1263–1272

    Article  CAS  PubMed  Google Scholar 

  120. Lee J, Liu L, Levin DE (2018) Stressing out or stressing in: intracellular pathways for SAPK activation. Current Genetics 1-5

  121. Metin M, Metin OK (2019) Cellular responses of Saccharomyces cerevisiae against arsenic. International Journal of Innovative Approaches in Science Research 3:41–52

    Article  Google Scholar 

  122. Xiong B, Zhang L, Xu H, Yang Y, Jiang L (2015) Cadmium induces the activation of cell wall integrity pathway in budding yeast. Chem Biol Interact 240:316–323

    Article  CAS  PubMed  Google Scholar 

  123. Kamada Y, Jung US, Piotrowski J, Levin DE (1995) The protein kinase C-activated MAP kinase pathway of Saccharomyces cerevisiae mediates a novel aspect of the heat shock response. Genes Dev 9:1559–1571

    Article  CAS  PubMed  Google Scholar 

  124. Sharma SK, Goloubinoff P, Christen P (2008) Heavy metal ions are potent inhibitors of protein folding. Biochem Biophys Res Commun 372:341–345

    Article  CAS  PubMed  Google Scholar 

  125. Tamás MJ, Sharma SK, Ibstedt S, Jacobson T, Christen P (2014) Heavy metals and metalloids as a cause for protein misfolding and aggregation. Biomolecules 4(1):252–267

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Jacobson T, Priya S, Sharma SK, Andersson S, Jakobsson S, Tanghe R, Christen P (2017) Cadmium causes misfolding and aggregation of cytosolic proteins in yeast. Mol Cell Biol MCB-00490

  127. Gidalevitz T, Ben-Zvi A, Ho KH, Brignull HR, Morimoto RI (2006) Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311:1471–1474

    Article  CAS  PubMed  Google Scholar 

  128. Holland S, Lodwig E, Sideri T, Reader T, Clarke I, Gkargkas K, Avery SV (2007) Application of the comprehensive set of heterozygous yeast deletion mutants to elucidate the molecular basis of cellular chromium toxicity. Genome Biol 8:268

    Article  CAS  Google Scholar 

  129. Ibstedt S, Sideri TC, Grant CM, Tamás MJ (2014) Global analysis of protein aggregation in yeast during physiological conditions and arsenite stress. Biology Open 3:913–923

    Article  PubMed  PubMed Central  Google Scholar 

  130. Plateau P, Saveanu C, Lestini R, Dauplais M, Decourty L, Jacquier A, Blanquet S, Lazard M (2017) Exposure to selenomethionine causes selenocysteine misincorporation and protein aggregation in Saccharomyces cerevisiae. Sci Rep 7:44761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Nikoleta GT, Daniel PR, Brown P (2012) The yeast rab GTPase Ypt1 modulates unfolded protein response dynamics by regulating the stability of HAC1 RNA. PLoS Genet 8(7):e1002862

    Article  CAS  Google Scholar 

  132. Hetz C, Chevet E, Oakes SA (2015) Proteostasis control by the unfolded protein response. Nat Cell Biol 17:829–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Kimata Y, Ishiwata-Kimata Y, Ito T, Hirata A, Suzuki T, Oikawa D, Kohno K (2007) Two regulatory steps of ER-stress sensor Ire1 involving its cluster formation and interaction with unfolded proteins. J Cell Biol 179:75–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Guerfal M, Ryckaert S, Jacobs P, Ameloot P, Van Craenenbroeck K, De Rycke R, Callewaert N (2010) The HAC1 gene from Pichia pastoris: characterization and effect of its overexpression on the production of secreted, surface displayed and membrane proteins. Microb Cell Factories 9(1):49

    Article  CAS  Google Scholar 

  135. Rüegsegger U, Leber JH, Walter P (2001) Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response. Cell 107:103–114

    Article  PubMed  Google Scholar 

  136. Cox JS, Walter P (1996) A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 87:391–404

    Article  CAS  PubMed  Google Scholar 

  137. Gardarin A, Chédin S, Lagniel G, Aude J, Godat E, Catty P, Labarre J (2010) Endoplasmic reticulum is a major target of cadmium toxicity in yeast. Mol Microbiol 76:1034–1048

    Article  CAS  PubMed  Google Scholar 

  138. Le QG, Ishiwata-Kimata Y, Kohno K, Kimata Y (2016) Cadmium impairs protein folding in the endoplasmic reticulum and induces the unfolded protein response. FEMS Yeast Research 16(5):fow049

  139. Goldberg AL (2003) Protein degradation and protection against misfolded or damaged proteins. Nature 426:895–899

    Article  CAS  PubMed  Google Scholar 

  140. Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451:1069–1075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Ciechanover A (2003) The ubiquitin proteolytic system and pathogenesis of human diseases: a novel platform for mechanism-based drug targeting. Portland Press Limited

  142. Glickman MH, Ciechanover A (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82:373–428

    Article  CAS  PubMed  Google Scholar 

  143. Shang F, Taylor A (2004) Function of the ubiquitin proteolytic pathway in the eye. Exp Eye Res 78:1–14

    Article  CAS  PubMed  Google Scholar 

  144. Shabek N, Herman-Bachinsky Y, Ciechanover A (2009) Ubiquitin degradation with its substrate, or as a monomer in a ubiquitination-independent mode, provides clues to proteasome regulation. Proc Natl Acad Sci 106:11907–11912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Hershko A, Ciechanover A (1998) The ubiquitin system. Annual Reviews 4139 El Camino Way, PO Box 10139, Palo Alto, CA 94303-0139, USA

  146. Nijman SMB, Luna-Vargas MPA, Velds A, Brummelkamp TR, Dirac AMG, Sixma TK, Bernards R (2005) A genomic and functional inventory of deubiquitinating enzymes. Cell 123:773–786

    Article  CAS  PubMed  Google Scholar 

  147. Wilkinson KD (2000) Ubiquitination and deubiquitination: targeting of proteins for degradation by the proteasome. Semin Cell Dev Biol 11:141–148

    Article  CAS  PubMed  Google Scholar 

  148. Lata S, Mishra R, Banerjea AC (2018) Proteasomal degradation machinery: favorite target of hiv-1 proteins. Front Microbiol 9:2738

    Article  PubMed  PubMed Central  Google Scholar 

  149. Jungmann J, Reins HA, Schobert C, Jentsch S (1993) Resistance to cadmium mediated by ubiquitin-dependent proteolysis. Nature 361:369–371

    Article  CAS  PubMed  Google Scholar 

  150. Baudouin-Cornu P, Labarre J (2006) Regulation of the cadmium stress response through SCF-like ubiquitin ligases: comparison between Saccharomyces cerevisiae, Schizosaccharomyces pombe and mammalian cells. Biochimie 88:1673–1685

    Article  CAS  PubMed  Google Scholar 

  151. Laferté A, Favry E, Sentenac A, Riva M, Carles C, Chédin S (2006) The transcriptional activity of RNA polymerase I is a key determinant for the level of all ribosome components. Genes Dev 20:2030–2040

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Rudra D, Warner JR (2004) What better measure than ribosome synthesis? Genes Dev 18:2431–2436

    Article  CAS  PubMed  Google Scholar 

  153. Jin YH, Dunlap PE, McBride SJ, Al-Refai H, Bushel PR, Freedman JH (2008) Global transcriptome and deletome profiles of yeast exposed to transition metals. PLoS Genet 4:e1000053

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Wang S, Shi X (2001) Molecular mechanisms of metal toxicity and carcinogenesis. Mol Cell Biochem 222(1–2):3–9

    Article  CAS  PubMed  Google Scholar 

  155. Zhou L, Le Roux G, Ducrot C, Chedin S, Labarre J, Riva M, Carles C (2013) Repression of class I transcription by cadmium is mediated by the protein phosphatase 2A. Nucleic Acids Res 41:6087–6097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Botany and Centre for Environmental Studies, Ege University, Izmir, Turkey

    Munir Ozturk

  2. Graduate School of Environmental Engineering, The University of Kitakyushu, 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan

    Mert Metin & Tomonori Kawano

  3. Department of Biology, Faculty of Science and Arts, Hatay Mustafa Kemal University, Antakya, Hatay, Turkey

    Volkan Altay

  4. School of Life Sciences, University of Technology Sydney, Sydney, 123, Australia

    Luigi De Filippis

  5. Faculty of Science and Arts, Department of Biotechnology, Nigde Omer Halisdemir University, Nigde, Turkey

    Bengu Turkyilmaz Ünal

  6. Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan

    Anum Khursheed

  7. Atta-ur-Rahman School of Applied Biosciences, National University of Sciences & Technology, Islamabad, Pakistan

    Alvina Gul

  8. Department of Agronomy, Faculty of Agriculture, Sher-e-Bangla Agricultural University, Dhaka, Bangladesh

    Mirza Hasanuzzaman

  9. Department of Agricultural Botany, Faculty of Agriculture, Sher-e-Bangla Agricultural University, Dhaka, Bangladesh

    Kamuran Nahar

  10. Agronomy Department of Superior School Engineering, University of Almería, Ctra. Sacramento s/n, La Cañadade San Urbano, 04120, Almería, Spain

    Pedro García Caparrós

Authors
  1. Munir Ozturk
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Mert Metin
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Volkan Altay
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Luigi De Filippis
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Bengu Turkyilmaz Ünal
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Anum Khursheed
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Alvina Gul
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Mirza Hasanuzzaman
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Kamuran Nahar
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Tomonori Kawano
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Pedro García Caparrós
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

The conception and design of the study: M.O., M.M., and V.A. Acquisition of data, analysis, and interpretation of data: M.O., M.M., V.A., B.T.U., A.K., A.G., M.H., K.N., T.K., and P.G.C. Drafting the article: M.O., M.M., V.A., A.K., A.G., M.H., K.N., and T.K. Revising the article critically for important intellectual content: M.O., V.A., A.K., A.G., M.H., K.N., and L.D. Final approval of the version to be submitted: M.O., V.A., and L.D.

Corresponding author

Correspondence to Munir Ozturk.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ozturk, M., Metin, M., Altay, V. et al. Molecular Biology of Cadmium Toxicity in Saccharomyces cerevisiae. Biol Trace Elem Res 199, 4832–4846 (2021). https://doi.org/10.1007/s12011-021-02584-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-021-02584-7

Keywords