The Antioxidant System in the Anhydrobiotic Midge as an Essential, Adaptive Mechanism for Desiccation Survival

  • Alexander Nesmelov
  • Richard Cornette
  • Oleg Gusev
  • Takahiro KikawadaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1081)


One of the major damaging factors for living organisms experiencing water insufficiency is oxidative stress. Loss of water causes a dramatic increase in the production of reactive oxygen species (ROS). Thus, the ability for some organisms to survive almost complete desiccation (called anhydrobiosis) is tightly related to the ability to overcome extraordinary oxidative stress. The most complex anhydrobiotic organism known is the larva of the chironomid Polypedilum vanderplanki. Its antioxidant system shows remarkable features, such as an expansion of antioxidant genes, their overexpression, as well as the absence or low expression of enzymes required for the synthesis of ascorbate and glutathione and their antioxidant function. In this chapter, we summarize existing data about the antioxidant system of this insect, which is able to cope with substantial oxidative damage, even in an intracellular environment that is severely disturbed due to water loss.


Anhydrobiosis P. vanderplanki Antioxidant Thioredoxin Glutathione peroxidase Superoxide dismutase 



Anhydrobiosis-related gene islands


Copper chaperone protein


Glutathione peroxidase






Reactive oxygen species


Superoxide dismutase




Thioredoxin reductase



We extend our gratitude to the Federal Ministry of Environment of Nigeria for permitting research on P. vanderplanki. The work was performed according to the Russian Government Program of Competitive Growth of Kazan Federal University and was supported by Russian Science Foundation grant for international group 14-44-00022. The work was also supported by JSPS KAKENHI Grant Numbers JP17H01511, JP16K07308, JP15H05622, JP25128714, and JP23128512.


  1. Bannai H, Tamada Y, Maruyama O, Nakai K, Miyano S (2002) Extensive feature detection of N-terminal protein sorting signals. Bioinformatics 18:298–305CrossRefGoogle Scholar
  2. Benaroudj N, Lee DH, Goldberg AL (2001) Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals. J Biol Chem 276:24261–24267CrossRefGoogle Scholar
  3. Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Kiefer F, Gallo Cassarino T, Bertoni M, Bordoli L et al (2014) SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 42:W252–W258CrossRefGoogle Scholar
  4. Brown NM, Torres AS, Doan PE, O’Halloran TV (2004) Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu, Zn superoxide dismutase. Proc Natl Acad Sci U S A 101:5518–5523CrossRefGoogle Scholar
  5. Buitink J, Leprince O (2004) Glass formation in plant anhydrobiotes: survival in the dry state. Cryobiology 48:215–228CrossRefGoogle Scholar
  6. Carroll MC, Girouard JB, Ulloa JL, Subramaniam JR, Wong PC, Valentine JS, Culotta VC (2004) Mechanisms for activating Cu- and Zn-containing superoxide dismutase in the absence of the CCS Cu chaperone. Proc Natl Acad Sci U S A 101:5964–5969CrossRefGoogle Scholar
  7. Cornette R, Kikawada T (2011) The induction of anhydrobiosis in the sleeping chironomid: current status of our knowledge. IUBMB Life 63:419–429CrossRefGoogle Scholar
  8. Cornette R, Kanamori Y, Watanabe M, Nakahara Y, Gusev O, Mitsumasu K, Kadono-Okuda K, Shimomura M, Mita K, Kikawada T et al (2010) Identification of anhydrobiosis-related genes from an expressed sequence tag database in the cryptobiotic midge Polypedilum vanderplanki (Diptera; Chironomidae). J Biol Chem 285:35889–35899CrossRefGoogle Scholar
  9. Cornette R, Yamamoto N, Yamamoto M, Kobayashi T, Petrova NA, Gusev O, Shimura S, Kikawada T, Pemba D, Okuda T (2017) A new anhydrobiotic midge from Malawi, Polypedilum pembai sp n. (Diptera: Chironomidae), closely related to the desiccation tolerant midge, Polypedilum vanderplanki Hinton. Syst Entomol 42:814–825CrossRefGoogle Scholar
  10. Corona M, Robinson GE (2006) Genes of the antioxidant system of the honey bee: annotation and phylogeny. Insect Mol Biol 15:687–701CrossRefGoogle Scholar
  11. Cranston PS (2014) A new putatively cryptobiotic midge, Polypedilum ovahimba sp nov (Diptera: Chironomidae), from southern Africa. Aust Entomol 53:373–379CrossRefGoogle Scholar
  12. Crowe JH (2007) Trehalose as a “chemical chaperone”: fact and fantasy. In: Csermely P, Vígh L (eds) Molecular aspects of the stress response: chaperones, membranes and networks. Springer, New York, pp 143–158CrossRefGoogle Scholar
  13. da Costa Morato Nery D, da Silva CG, Mariani D, Fernandes PN, Pereira MD, Panek AD, Eleutherio EC (2008) The role of trehalose and its transporter in protection against reactive oxygen species. Biochim Biophys Acta 1780:1408–1411CrossRefGoogle Scholar
  14. Emanuelsson O, Nielsen H, Brunak S, von Heijne G (2000) Predicting subcellular localization of proteins based on their N-terminal amino acid sequence. J Mol Biol 300:1005–1016CrossRefGoogle Scholar
  15. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247CrossRefGoogle Scholar
  16. Foyer CH, Noctor G (2011) Ascorbate and glutathione: the heart of the redox hub. Plant Physiol 155:2–18CrossRefGoogle Scholar
  17. França MB, Panek AD, Eleutherio EC (2007) Oxidative stress and its effects during dehydration. Comp Biochem Physiol A Mol Integr Physiol 146:621–631CrossRefGoogle Scholar
  18. Furukawa Y, Torres AS, O'Halloran TV (2004) Oxygen-induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS. EMBO J 23:2872–2881CrossRefGoogle Scholar
  19. Grubor-Lajsic G, Block W, Jovanovic A, Worland R (1996) Antioxidant enzymes in larvae of the Antarctic fly, Belgica antarctica. CryoLetters 17:39–42Google Scholar
  20. Gusev O, Nakahara Y, Vanyagina V, Malutina L, Cornette R, Sakashita T, Hamada N, Kikawada T, Kobayashi Y, Okuda T (2010) Anhydrobiosis-associated nuclear DNA damage and repair in the sleeping chironomid: linkage with radioresistance. PLoS One 5:e14008CrossRefGoogle Scholar
  21. Gusev O, Suetsugu Y, Cornette R, Kawashima T, Logacheva MD, Kondrashov AS, Penin AA, Hatanaka R, Kikuta S, Shimura S et al (2014) Comparative genome sequencing reveals genomic signature of extreme desiccation tolerance in the anhydrobiotic midge. Nat Commun 5:4784CrossRefGoogle Scholar
  22. Herdeiro RS, Pereira MD, Panek AD, Eleutherio EC (2006) Trehalose protects Saccharomyces cerevisiae from lipid peroxidation during oxidative stress. Biochim Biophys Acta 1760:340–346CrossRefGoogle Scholar
  23. Hinton H (1951) A new Chironomid from Africa, the larva of which can be dehydrated without injury. Proc Zool Soc Lond 121:371–380CrossRefGoogle Scholar
  24. Hinton H (1960) A fly larva that tolerates dehydration and temperatures of −270° to +102° C. Nature 188:336–337CrossRefGoogle Scholar
  25. Holmgren A, Sengupta R (2010) The use of thiols by ribonucleotide reductase. Free Radic Biol Med 49:1617–1628CrossRefGoogle Scholar
  26. Indo HP, Davidson M, Yen HC, Suenaga S, Tomita K, Nishii T, Higuchi M, Koga Y, Ozawa T, Majima HJ (2007) Evidence of ROS generation by mitochondria in cells with impaired electron transport chain and mitochondrial DNA damage. Mitochondrion 7:106–118CrossRefGoogle Scholar
  27. Jensen LT, Culotta VC (2005) Activation of CuZn superoxide dismutases from Caenorhabditis elegans does not require the copper chaperone CCS. J Biol Chem 280:41373–41379CrossRefGoogle Scholar
  28. Lartigue A, Burlat B, Coutard B, Chaspoul F, Claverie JM, Abergel C (2015) The Megavirus chilensis Cu, Zn-superoxide dismutase: the first viral structure of a typical cellular copper chaperone-independent hyperstable dimeric enzyme. J Virol 89:824–832CrossRefGoogle Scholar
  29. Leitch JM, Yick PJ, Culotta VC (2009) The right to choose: multiple pathways for activating copper, zinc superoxide dismutase. J Biol Chem 284:24679–24683CrossRefGoogle Scholar
  30. Leprince O, Atherton NM, Deltour R, Hendry G (1994) The involvement of respiration in free radical processes during loss of desiccation tolerance in germinating Zea mays L. (an electron paramagnetic resonance study). Plant Physiol 104:1333–1339CrossRefGoogle Scholar
  31. Lopez-Martinez G, Elnitsky MA, Benoit JB, Lee RE Jr, Denlinger DL (2008) High resistance to oxidative damage in the Antarctic midge Belgica antarctica, and developmentally linked expression of genes encoding superoxide dismutase, catalase and heat shock proteins. Insect Biochem Mol Biol 38:796–804CrossRefGoogle Scholar
  32. Maiorino M, Ursini F, Bosello V, Toppo S, Tosatto SC, Mauri P, Becker K, Roveri A, Bulato C, Benazzi L et al (2007) The thioredoxin specificity of Drosophila GPx: a paradigm for a peroxiredoxin-like mechanism of many glutathione peroxidases. J Mol Biol 365:1033–1046CrossRefGoogle Scholar
  33. Meyer Y, Siala W, Bashandy T, Riondet C, Vignols F, Reichheld JP (2008) Glutaredoxins and thioredoxins in plants. Biochim Biophys Acta 1783:589–600CrossRefGoogle Scholar
  34. Nair PM, Park SY, Chung JW, Choi J (2013) Transcriptional regulation of glutathione biosynthesis genes, gamma-glutamyl-cysteine ligase and glutathione synthetase in response to cadmium and nonylphenol in Chironomus riparius. Environ Toxicol Pharmacol 36:265–273CrossRefGoogle Scholar
  35. Nakahara Y, Imanishi S, Mitsumasu K, Kanamori Y, Iwata K, Watanabe M, Kikawada T, Okuda T (2010) Cells from an anhydrobiotic chironomid survive almost complete desiccation. Cryobiology 60:138–146CrossRefGoogle Scholar
  36. Nesmelov A, Devatiyarov R, Voronina T, Kondratyeva S, Cherkasov A, Cornette R, Kikawada T, Shagimardanova E (2016) New antioxidant genes from an anhydrobiotic insect: unique structural features in functional motifs of thioredoxins. BioNanoScience 6:568–570CrossRefGoogle Scholar
  37. Oku K, Watanabe H, Kubota M, Fukuda S, Kurimoto M, Tsujisaka Y, Komori M, Inoue Y, Sakurai M (2003) NMR and quantum chemical study on the OH···π and CH···O interactions between trehalose and unsaturated fatty acids: implication for the mechanism of antioxidant function of trehalose. J Am Chem Soc 125:12739–12748CrossRefGoogle Scholar
  38. Patenaude A, Ven Murthy MR, Mirault ME (2004) Mitochondrial thioredoxin system: effects of TrxR2 overexpression on redox balance, cell growth, and apoptosis. J Biol Chem 279:27302–27314CrossRefGoogle Scholar
  39. Pereira Ede J, Panek AD, Eleutherio EC (2003) Protection against oxidation during dehydration of yeast. Cell Stress Chaperones 8:120–124CrossRefGoogle Scholar
  40. Petersen TN, Brunak S, von Heijne G, Nielsen H (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods 8:785–786CrossRefGoogle Scholar
  41. Pompella A, Visvikis A, Paolicchi A, De Tata V, Casini AF (2003) The changing faces of glutathione, a cellular protagonist. Biochem Pharmacol 66:1499–1503CrossRefGoogle Scholar
  42. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49:1603–1616CrossRefGoogle Scholar
  43. Sakurai M, Furuki T, Akao K, Tanaka D, Nakahara Y, Kikawada T, Watanabe M, Okuda T (2008) Vitrification is essential for anhydrobiosis in an African chironomid, Polypedilum vanderplanki. Proc Natl Acad Sci U S A 105:5093–5098CrossRefGoogle Scholar
  44. Scheerer P, Borchert A, Krauss N, Wessner H, Gerth C, Hohne W, Kuhn H (2007) Structural basis for catalytic activity and enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4 (GPx4). Biochemistry 46:9041–9049CrossRefGoogle Scholar
  45. Sun WQ, Leopold AC (1995) The Maillard reaction and oxidative stress during aging of soybean seeds. Physiol Plant 94:94–104CrossRefGoogle Scholar
  46. Uttara B, Singh AV, Zamboni P, Mahajan R (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7:65–74CrossRefGoogle Scholar
  47. Watanabe M, Kikawada T, Minagawa N, Yukuhiro F, Okuda T (2002) Mechanism allowing an insect to survive complete dehydration and extreme temperatures. J Exp Biol 205:2799–2802PubMedGoogle Scholar
  48. Watanabe M, Kikawada T, Fujita A, Okuda T (2005) Induction of anhydrobiosis in fat body tissue from an insect. J Insect Physiol 51:727–731CrossRefGoogle Scholar
  49. Watanabe M, Nakahara Y, Sakashita T, Kikawada T, Fujita A, Hamada N, Horikawa DD, Wada S, Kobayashi Y, Okuda T (2007) Physiological changes leading to anhydrobiosis improve radiation tolerance in Polypedilum vanderplanki larvae. J Insect Physiol 53:573–579CrossRefGoogle Scholar
  50. Weisiger RA, Fridovich I (1973) Mitochondrial superoxide dismutase site of synthesis and intramitochondrial localization. J Biol Chem 248:4793–4796PubMedGoogle Scholar
  51. Zelko IN, Mariani TJ, Folz RJ (2002) Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med 33:337–349CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Alexander Nesmelov
    • 1
  • Richard Cornette
    • 2
  • Oleg Gusev
    • 1
    • 3
  • Takahiro Kikawada
    • 2
    • 4
    Email author
  1. 1.Kazan Federal UniversityKazanRussia
  2. 2.Molecular Biomimetics Research Unit, Institute of Agrobiological SciencesNAROTsukubaJapan
  3. 3.RIKEN Center for Life Science TechnologiesRIKENYokohamaJapan
  4. 4.Graduate School of Frontier SciencesThe University of TokyoChibaJapan

Personalised recommendations