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5′-AMP-Activated Protein Kinase Signaling in Caenorhabditis elegans

  • Moloud Ahmadi
  • Richard RoyEmail author
Chapter
Part of the Experientia Supplementum book series (EXS, volume 107)

Abstract

AMP-activated protein kinase (AMPK) is one of the central regulators of cellular and organismal metabolism in eukaryotes. Once activated by decreased energy levels, it induces ATP production by promoting catabolic pathways while conserving ATP by inhibiting anabolic pathways. AMPK plays a crucial role in various aspects of cellular function such as regulating growth, reprogramming metabolism, autophagy, and cell polarity. In this chapter, we focus on how recent breakthroughs made using the model organism Caenorhabditis elegans have contributed to our understanding of AMPK function and how it can be utilized in the future to elucidate hitherto unknown aspects of AMPK signaling.

Keywords

AMPK AAK-2 Caenorhabditis elegans Diapause Dauer Germline stem cell quiescence Lifespan Longevity 

References

  1. Apfeld J, O'Connor G, McDonagh T, DiStefano PS, Curtis R (2004) The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev 15:3004–9CrossRefGoogle Scholar
  2. Avruch J, Hara K, Lin Y, Liu M, Long X, Ortiz-Vega S, Yonezawa K (2006) Insulin and amino-acid regulation of mTOR signalling and kinase activity through the Rheb GTPase. Oncogene 16:6361–6372CrossRefGoogle Scholar
  3. Bargmann CI (2006) Chemosensation in C. elegans. Worm BookGoogle Scholar
  4. Baugh LR, Sternberg PW (2006) DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest. Curr Biol 16:780–785CrossRefPubMedGoogle Scholar
  5. Beale EG (2008) 5′-AMP-activated protein kinase signalling in Caenorhabditis elegans. Exp Biol Med (Maywood) 233:12–20CrossRefGoogle Scholar
  6. Ben-Zvi A, Miller EA, Morimoto RI (2009) Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. Proc Natl Acad Sci 106:14914–14919CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bordone L, Guarente L (2005) Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 6:298–305CrossRefPubMedGoogle Scholar
  8. Burkewitz K, Morantte I, Weir HJM, Yeo R, Zhang Y, Huynh FK, Ilkayeva OR, Hirschey MD, Grant AR, Mair WB (2015) Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal. Cell 160:842–855CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chen D, Li PW, Goldstein BA, Cai W, Thomas EL, Chen F, Hubbard AE, Melov S, Kapahi P (2013) Germline signalling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans. Cell Rep 5:1600–1610CrossRefPubMedPubMedCentralGoogle Scholar
  10. Cunningham KA, Ashrafi K (2009) Fat rationing in dauer times. Cell Metab 9:113–114CrossRefPubMedGoogle Scholar
  11. Cunningham KA, Hua Z, Srinivasan S, Liu J, Lee BH, Edwards RH, Ashrafi K (2012) AMP-activated kinase links serotonergic signaling to glutamate release for regulation of feeding behavior in C. elegans. Cell Metab 16:113–121CrossRefPubMedPubMedCentralGoogle Scholar
  12. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11–20CrossRefPubMedGoogle Scholar
  13. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM, Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ (2011) Phosphorylation of ULK1 (hATG1) by AMP activated protein kinase connects energy sensing to mitophagy. Science 331:456–461CrossRefPubMedGoogle Scholar
  14. Fielenbach N, Antebi AC (2008) C. elegans dauer formation and the molecular basis of plasticity. Genes Dev 22:2149–2165CrossRefPubMedPubMedCentralGoogle Scholar
  15. Finch CE (1994) Longevity, senescence and the genome. University of Chicago Press, ChicagoGoogle Scholar
  16. Florez-McClure ML, Hohsfield LA, Fonte G, Bealor MT, Link CD (2007) Decreased insulin-receptor signalling promotes the autophagic degradation of beta-amyloid peptide in C. elegans. Autophagy 3:569–580CrossRefPubMedGoogle Scholar
  17. Fukuyama M, Sakuma K, Park R, Kasuga H, Nagaya R, Atsumi Y, Shimomura Y, Takahashi S, Kajiho H, Rougvie A, Kontani K, Katada T (2012) C. elegans AMPKs promote survival and arrest germline development during nutrient stress. Biol Open 1:929–936CrossRefPubMedPubMedCentralGoogle Scholar
  18. Greer EL, Brunet A (2009) Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans. Aging Cell 8:113–127CrossRefPubMedPubMedCentralGoogle Scholar
  19. Greer EL, Dowlatshahi D, Banko MR, Villen J, Hoang K, Blanchard D, Gygi SP, Brunet A (2007) An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr Biol 17:1646–1656CrossRefPubMedPubMedCentralGoogle Scholar
  20. Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30:214–226CrossRefPubMedPubMedCentralGoogle Scholar
  21. Haesa WD, Frooninckxa L, Asschea RV, Smoldersb A, Depuydta G, Billenc J, Braeckmanb BP, Schoofsa L, Temmermana L (2014) Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2. Proc Natl Acad Sci 111:2501–2509CrossRefGoogle Scholar
  22. Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, Kenyon C (2007) Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6:95–110CrossRefPubMedGoogle Scholar
  23. Hardie DG (2011) AMP-activated protein kinase—an energy sensor that regulates all aspects of cell function. Genes Dev 25:1895–1908CrossRefPubMedPubMedCentralGoogle Scholar
  24. Hekimi S, Guarente L (2003) Genetics and the specificity of the aging process. Science 299:1351–1354CrossRefPubMedGoogle Scholar
  25. Hertweck M, Göbel C, Baumeister RC (2004) C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell 6:577–88CrossRefPubMedGoogle Scholar
  26. Hirsh D, Oppenheim D, Klass M (1976) Development of the reproductive system of Caenorhabditis elegans. Dev Biol 49:200–219CrossRefPubMedGoogle Scholar
  27. Honjoh S, Yamamoto T, Uno M, Nishida E (2009) Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans. Nature 457:726–730CrossRefPubMedGoogle Scholar
  28. Hu PJ (2005) The online review of C. elegans biology. Worm BookGoogle Scholar
  29. Hubbard EJ, Korta DZ, Dalfó D (2013) Physiological control of germline development. Adv Exp Med Biol 757:101–131CrossRefPubMedPubMedCentralGoogle Scholar
  30. Jia K, Chen D, Riddle DL (2004) The TOR pathway interacts with the insulin signalling pathway to regulate C. elegans larval development, metabolism and life span. Development 131:3897–3906CrossRefPubMedGoogle Scholar
  31. Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW, Thomas EL, Kockel L (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11:453–465CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461–464CrossRefPubMedGoogle Scholar
  33. Killian DJ, Hubbard EJA (2004) C. elegans pro-1 activity is required for soma/germline interactions that influence proliferation and differentiation in the germ line. Development 131:1267–1278CrossRefPubMedGoogle Scholar
  34. Killian DJ, Hubbard EJA (2005) Caenorhabditis elegans germline patterning requires coordinated development of the somatic gonadal sheath and the germ line. Dev Biol 279:322–335CrossRefPubMedGoogle Scholar
  35. Kimble J, Hirsh D (1979) The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans. Dev Biol 70:396–417CrossRefPubMedGoogle Scholar
  36. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277:942–946CrossRefPubMedGoogle Scholar
  37. Lapierre LR, Gelino S, Meléndez A, Hansen M (2011) Autophagy and lipid metabolism coordinately modulate life span in germline-less C. elegans. Curr Biol 21:1507–1514CrossRefPubMedPubMedCentralGoogle Scholar
  38. Lee H, Cho JS, Lambacher N, Lee J, Lee S, Lee TH, Gartner A, Koo H (2008) The Caenorhabditis elegans AMP-activated protein kinase AAK-2 is phosphorylated by LKB1 and is required for resistance to oxidative stress and for normal motility and foraging behavior. J Biol Chem 283:14988–14993CrossRefPubMedPubMedCentralGoogle Scholar
  39. Lemieux GA, Cunningham KA, Lin L, Mayer F, Werb Z, Ashrafi K (2015) Kynurenic acid is a nutritional cue that enables behavioral plasticity. Cell 160:119–131CrossRefPubMedPubMedCentralGoogle Scholar
  40. Lin K, Dorman JB, Rodan A, Kenyon C (1997) daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278:1319–22CrossRefPubMedGoogle Scholar
  41. Longo VD, Finch CE (2003) Evolutionary medicine: from dwarf model systems to healthy centenarians. Science 299:1342–1346CrossRefPubMedGoogle Scholar
  42. Mair W, Morantte I, Rodrigues AP, Manning G, Montminy M, Shaw RJ, Dillin A (2011) A Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB. Nature 470:404–408CrossRefPubMedPubMedCentralGoogle Scholar
  43. Mihaylova MM, Shaw RJ (2011) The AMP-activated protein kinase (AMPK) signalling pathway coordinates cell growth, autophagy, & metabolism. Nat Cell Biol 13:1016–1023CrossRefPubMedPubMedCentralGoogle Scholar
  44. Morris JZ, Tissenbaum HA, Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382:536–9CrossRefPubMedGoogle Scholar
  45. Narbonne P, Roy R (2006) Inhibition of germline proliferation during C. elegans dauer development requires PTEN, LKB1 and AMPK signalling. Development 133:61–619CrossRefGoogle Scholar
  46. Narbonne P, Roy R (2009) Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival. Nature 457:210–214CrossRefPubMedGoogle Scholar
  47. Narbonne P, Hyenne V, Li S, Labbé J, Roy R (2010) Differential requirements for STRAD in LKB1-dependent functions in C. elegans. Development 137:661–670CrossRefPubMedGoogle Scholar
  48. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389:994–999CrossRefPubMedGoogle Scholar
  49. Onken B, Driscoll M (2010) Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans healthspan via AMPK, LKB1, and SKN-1. PLoS One 5, e8758CrossRefPubMedPubMedCentralGoogle Scholar
  50. Paradis S, Ruvkun G (1998) Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev 12:2488–2498CrossRefPubMedPubMedCentralGoogle Scholar
  51. Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, Néri C (2005) Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet 37:349–50CrossRefPubMedGoogle Scholar
  52. Robida-Stubbs S, Glover-Cutter K, Lamming DW, Mizunuma M, Narasimhan SD, Neumann-Haefelin E, Sabatini DM, Blackwell TK (2012) TOR signalling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab 15:713–724CrossRefPubMedPubMedCentralGoogle Scholar
  53. Schmeisser S, Priebe S, Groth M, Monajembashi S, Hemmerich P, Guthke R, Platzer M, Ristow M (2013) Neuronal ROS signalling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension. Mol Metab 2:92–102CrossRefPubMedPubMedCentralGoogle Scholar
  54. Schreiber MA, Pierce-Shimomura JT, Chan S, Parry D, McIntire SL (2010) Manipulation of behavioral decline in Caenorhabditis elegans with the Rag GTPase raga-1. PLoS Genet 6, e1000972CrossRefPubMedPubMedCentralGoogle Scholar
  55. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–11CrossRefPubMedGoogle Scholar
  56. Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007) Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab 6:280–293CrossRefPubMedGoogle Scholar
  57. Shackelford DB, Vasquez DS, Corbeil J, Wu S, Leblanc M, Wu CL, Vera DR, Shaw RJ (2009) mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome. Proc Natl Acad Sci 106:11137–11142CrossRefPubMedPubMedCentralGoogle Scholar
  58. Sigmond T, Barna J, Tóth ML, Takács-Vellai K, Pásti G, Kovács AL, Vellai T (2008) Autophagy in Caenorhabditis elegans. Methods Enzymol 451:521–540CrossRefPubMedGoogle Scholar
  59. Tobin DV, Saito RM (2012) Developmental decisions: Balancing genetics and the environment by C. elegans. Cell Cycle 11:1666–1671CrossRefPubMedPubMedCentralGoogle Scholar
  60. Tullet JM, Araiz C, Sanders MJ, Au C, Benedetto A, Papatheodorou I, Clark E, Schmeisser K, Jones D, Schuster EF, Thornton JM, Gems D (2014) DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of Insulin/IGF-1 signalling on aging in Caenorhabditis elegans. PLoS Genet 10, e1004109CrossRefPubMedPubMedCentralGoogle Scholar
  61. Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Müller F (2003) Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426:620CrossRefPubMedGoogle Scholar
  62. Wood WB, Hecht R, Carr S, Vanderslice R, Wolf N, Hirsh D (1980) Parental effects and phenotypic characterization of mutations that affect early development in Caenorhabditis elegans. Dev Biol 74:446–469CrossRefPubMedGoogle Scholar
  63. Xie M, Roy R (2012) Increased levels of hydrogen peroxide induce a HIF-1-dependent modification of lipid metabolism in AMPK compromised C. elegans dauer larvae. Cell Metab 16:322–35CrossRefPubMedGoogle Scholar
  64. Xie M, Roy R (2015) AMP-Activated kinase regulates lipid droplet localization and stability of adipose triglyceride lipase in C. elegans dauer larvae. Plos One 10:e0130480Google Scholar
  65. Yee C, Yang W, Hekimi S (2014) The pro-longevity response to mitochondrial ROS in C. elegans is mediated by the intrinsic apoptosis pathway. Cell 157:897–909CrossRefPubMedPubMedCentralGoogle Scholar
  66. Zarse K, Schmeisser S, Groth M, Priebe S, Beuster G, Kuhlow D, Guthke R, Platzer M, Kahn CR, Ristow M (2012) Impaired insulin/IGF1 signalling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell Metab 15:451–65CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of BiologyMcGill UniversityMontrealCanada

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