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Current Genetics

, Volume 65, Issue 2, pp 339–349 | Cite as

Circadian rhythms, metabolic oscillators, and the target of rapamycin (TOR) pathway: the Neurospora connection

  • Patricia Lakin-ThomasEmail author
Review

Abstract

Circadian (24-h) rhythmicity is a fundamental property of eukaryotic cells, and it is not surprising that it intersects with fundamental metabolic processes. Many links between these two processes have been documented, and speculation has been growing that there may be circadian “metabolic oscillators” that interact with and exist independently of the well-known circadian transcription/translation feedback loops (TTFLs) that have been extensively studied. This review takes a critical look at the evidence for the existence of metabolic oscillators at the cellular level, attempting to answer these questions: does metabolism affect circadian rhythmicity, and vice versa? Is metabolism rhythmic, and if so, is that rhythmicity cell autonomous? Systems displaying “non-canonical rhythmicity” in the absence of functional TTFLs provide opportunities for identifying metabolic oscillators, and this review emphasizes the fungus Neurospora crassa as a model system. Recent papers describing links between the target of rapamycin (TOR) signaling pathway and circadian rhythmicity are highlighted, suggesting the potential for TOR signaling in generating rhythmicity independent of TTFLs.

Keywords

Circadian Metabolism Neurospora crassa Target of rapamycin Oscillator 

Notes

Acknowledgements

Funding provided by Natural Sciences and Engineering Research Council, Canada, Discovery Grant 2017-05664. Thanks to Stuart Brody and Lalanthi Ratnayake for helpful comments on the manuscript.

References

  1. Adhvaryu K, Firoozi G, Motavaze K, Lakin-Thomas P (2016) PRD-1, a component of the circadian system of Neurospora crassa, is a member of the DEAD-box RNA helicase family. J Biol Rhythms 31:258–271.  https://doi.org/10.1177/0748730416639717 CrossRefGoogle Scholar
  2. Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, Walter P (2015) Molecular biology of the cell, 6th edn. Garland Science, New YorkGoogle Scholar
  3. Bass J (2012) Circadian topology of metabolism. Nature 491:348–356.  https://doi.org/10.1038/nature11704 CrossRefGoogle Scholar
  4. Belden WJ, Larrondo LF, Froehlich AC, Shi M, Chen CH, Loros JJ, Dunlap JC (2007) The band mutation in Neurospora crassa is a dominant allele of ras-1 implicating RAS signaling in circadian output. Genes Dev 21:1494–1505.  https://doi.org/10.1101/gad.1551707 CrossRefGoogle Scholar
  5. Brody S (1992) Circadian rhythms in Neurospora crassa: the role of mitochondria. Chronobiol Int 9:222–230.  https://doi.org/10.3109/07420529209064531 CrossRefGoogle Scholar
  6. Brody S, Harris S (1973) Circadian rhythms in Neurospora—spatial differences in pyridine nucleotide levels. Science 180:498–500.  https://doi.org/10.1126/science.180.4085.498 CrossRefGoogle Scholar
  7. Cao R (2018) mTOR signaling, translational control, and the circadian clock. Front Genet.  https://doi.org/10.3389/fgene.2018.00367 Google Scholar
  8. Cao R, Anderson FE, Jung YJ, Dziema H, Obrietan K (2011) Circadian regulation of mammalian target of rapamycin signaling in the mouse suprachiasmatic nucleus. Neuroscience 181:79–88.  https://doi.org/10.1016/j.neuroscience.2011.03.005 CrossRefGoogle Scholar
  9. Cao R, Robinson B, Xu H, Gkogkas C, Khoutorsky A, Alain T, Yanagiya A, Nevarko T, Liu A, Amir S, Sonenberg N (2013) Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling. Neuron 79:712–724.  https://doi.org/10.1016/j.neuron.2013.06.026 CrossRefGoogle Scholar
  10. Causton HC, Feeney KA, Ziegler CA, O’Neill JS (2015) Metabolic cycles in yeast share features conserved among circadian rhythms. Curr Biol 25:1056–1062.  https://doi.org/10.1016/j.cub.2015.02.035 CrossRefGoogle Scholar
  11. Cho CS, Yoon HJ, Kim JY, Woo HA, Rhee SG (2014) Circadian rhythm of hyperoxidized peroxiredoxin II is determined by hemoglobin autoxidation and the 20S proteasome in red blood cells. Proc Natl Acad Sci USA 111:12043–12048.  https://doi.org/10.1073/pnas.1401100111 CrossRefGoogle Scholar
  12. Dibner C, Schibler U (2015) Circadian timing of metabolism in animal models and humans. J Intern Med 277:513–527.  https://doi.org/10.1111/joim.12347 CrossRefGoogle Scholar
  13. Dyar KA, Eckel-Mahan KL (2017) Circadian metabolomics in time and space. Front Neurosci.  https://doi.org/10.3389/fnins.2017.00369 Google Scholar
  14. Edgar RS, Green EW, Zhao Y, Van Ooijen G, Olmedo M, Qin X, Xu Y, Pan M, Valekunja UK, Feeney KA, Maywood ES, Hastings MH, Baliga NS, Merrow M, Millar AJ, Johnson CH, Kyriacou CP, O’Neill JS, Reddy AB (2012) Peroxiredoxins are conserved markers of circadian rhythms. Nature 485:459–464.  https://doi.org/10.1038/nature11088 CrossRefGoogle Scholar
  15. Eltschinger S, Loewith R (2016) TOR complexes and the maintenance of cellular homeostasis. Trends Cell Biol 26:148–159.  https://doi.org/10.1016/j.tcb.2015.10.003 CrossRefGoogle Scholar
  16. Emerson JM, Bartholomai BM, Ringelberg CS, Baker SE, Loros JJ, Dunlap JC (2015) Period-1 encodes an ATP-dependent RNA helicase that influences nutritional compensation of the Neurospora circadian clock. Proc Natl Acad Sci USA 112:15707–15712.  https://doi.org/10.1073/pnas.1521918112 Google Scholar
  17. Ghosh A, Chance B (1964) Oscillations of glycolytic intermediates in yeast cells. Biochem Biophys Res Commun 16:174–181.  https://doi.org/10.1016/0006-291X(64)90357-2 CrossRefGoogle Scholar
  18. Goodwin BC (1965) Oscillatory behavior in enzymatic control processes. Pergamon Press, OxfordCrossRefGoogle Scholar
  19. Gyöngyösi N, Nagy D, Makara K, Ella K, Káldi K (2013) Reactive oxygen species can modulate circadian phase and period in Neurospora crassa. Free Radic Biol Med 58:134–143.  https://doi.org/10.1016/j.freeradbiomed.2012.12.016 CrossRefGoogle Scholar
  20. Gyöngyösi N, Szoke A, Ella K, Káldi K (2017) The small G protein RAS2 is involved in the metabolic compensation of the circadian clock in the circadian model Neurospora crassa. J Biol Chem 292:14929–14939.  https://doi.org/10.1074/jbc.M117.804922 CrossRefGoogle Scholar
  21. Henslee EA, Crosby P, Kitcatt SJ, Parry JSW, Bernardini A, Abdallat RG, Braun G, Fatoyinbo HO, Harrison EJ, Edgar RS, Hoettges KF, Reddy AB, Jabr RI, Von Schantz M, O’Neill JS, Labeed FH (2017) Rhythmic potassium transport regulates the circadian clock in human red blood cells. Nature Commun.  https://doi.org/10.1038/s41467-017-02161-4 Google Scholar
  22. Huang CCY, Ko ML, Ko GYP (2013) A new functional role for mechanistic/mammalian target of rapamycin complex 1 (mTORC1) in the circadian regulation of L-type voltage-gated calcium channels in avian cone photoreceptors. PLoS One.  https://doi.org/10.1371/journal.pone.0073315 Google Scholar
  23. Hurley JM, Dasgupta A, Emerson JM, Zhou X, Ringelberg CS, Knabe N, Lipzen AM, Lindquist EA, Daum CG, Barry KW, Grigoriev IV, Smith KM, Galagan JE, Bell-Pedersen D, Freitag M, Cheng C, Lorosa JJ, Dunlap JC (2014) Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential. Proc Natl Acad Sci USA 111:16995–17002.  https://doi.org/10.1073/pnas.1418963111 CrossRefGoogle Scholar
  24. Hurley JM, Loros JJ, Dunlap JC (2016) The circadian system as an organizer of metabolism. Fungal Genet Biol 90:39–43.  https://doi.org/10.1016/j.fgb.2015.10.002 CrossRefGoogle Scholar
  25. Iwasaki H, Dunlap JC (2000) Microbial circadian oscillatory systems in Neurospora and Synechococcus: models for cellular clocks. Curr Opin Microbiol 3:189–196.  https://doi.org/10.1016/S1369-5274(00)00074-6 CrossRefGoogle Scholar
  26. Krishnaiah SY, Wu G, Altman BJ, Growe J, Rhoades SD, Coldren F, Venkataraman A, Olarerin-George AO, Francey LJ, Mukherjee S, Girish S, Selby CP, Cal S, Er U, Sianati B, Sengupta A, Anafi RC, Kavakli IH, Sancar A, Baur JA, Dang CV, Hogenesch JB, Weljie AM (2017) Clock regulation of metabolites reveals coupling between transcription and metabolism. Cell Metab 25:961–974.  https://doi.org/10.1016/j.cmet.2017.03.019 CrossRefGoogle Scholar
  27. Kumar Jha P, Challet E, Kalsbeek A (2015) Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals. Mol Cell Endocrinol 418:74–88.  https://doi.org/10.1016/j.mce.2015.01.024 CrossRefGoogle Scholar
  28. Kurz FT, Kembro JM, Flesia AG, Armoundas AA, Cortassa S, Aon MA, Lloyd D (2017) Network dynamics: quantitative analysis of complex behavior in metabolism, organelles, and cells, from experiments to models and back. Wiley Interdiscip Rev Syst Biol Med.  https://doi.org/10.1002/wsbm.1352 Google Scholar
  29. Lakin-Thomas PL (1996) Effects of choline depletion on the circadian rhythm in Neurospora crassa. Biol Rhythm Res 27:12–30.  https://doi.org/10.1076/brhm.27.1.12.12933 CrossRefGoogle Scholar
  30. Lakin-Thomas PL (1998) Choline depletion, frq mutations, and temperature compensation of the circadian rhythm in Neurospora crassa. J Biol Rhythms 13:268–277.  https://doi.org/10.1177/074873098129000101 CrossRefGoogle Scholar
  31. Lakin-Thomas PL (2006) Circadian clock genes frequency and white collar-1 are not essential for entrainment to temperature cycles in Neurospora crassa. Proc Natl Acad Sci USA 103:4469–4474.  https://doi.org/10.1073/pnas.0510404103 CrossRefGoogle Scholar
  32. Lakin-Thomas PL, Brody S (1985) Circadian rhythms in Neurospora crassa: interactions between clock mutations. Genetics 109:49–66Google Scholar
  33. Lakin-Thomas PL, Brody S (2000) Circadian rhythms in Neurospora crassa: lipid deficiencies restore robust rhythmicity to null frequency and white-collar mutants. Proc Natl Acad Sci USA 97:256–261.  https://doi.org/10.1073/pnas.97.1.256 CrossRefGoogle Scholar
  34. Lakin-Thomas PL, Cote GG, Brody S (1990) Circadian rhythms in Neurospora crassa: biochemistry and genetics. Crit Rev Microbiol 17:365–416.  https://doi.org/10.3109/10408419009114762 CrossRefGoogle Scholar
  35. Lakin-Thomas P, Bell-Pedersen D, Brody S (2011) The genetics of circadian rhythms in Neurospora. In: Brody S (ed) The genetics of circadian rhythms. advances in genetics, vol 74. Elsevier, Amsterdam, pp 55–104CrossRefGoogle Scholar
  36. Larrondo LF, Olivares-Yañez C, Baker CL, Loros JJ, Dunlap JC (2015) Decoupling circadian clock protein turnover from circadian period determination. Science.  https://doi.org/10.1126/science.1257277 Google Scholar
  37. Li S, Lakin-Thomas PL (2010) Effects of prd circadian clock mutations on FRQ-less rhythms in Neurospora. J Biol Rhythms 25:71–80.  https://doi.org/10.1177/0748730409360889 CrossRefGoogle Scholar
  38. Li S, Motavaze K, Kafes E, Suntharalingam S, Lakin-Thomas P (2011) A new mutation affecting FRQ-less rhythms in the circadian system of Neurospora crassa. PLoS Genet.  https://doi.org/10.1371/journal.pgen.1002151 Google Scholar
  39. Lipton JO, Boyle LM, Yuan ED, Hochstrasser KJ, Chifamba FF, Nathan A, Tsai PT, Davis F, Sahin M (2017) Aberrant proteostasis of BMAL1 underlies circadian abnormalities in a paradigmatic mTOR-opathy. Cell Rep 20:868–880.  https://doi.org/10.1016/j.celrep.2017.07.008 CrossRefGoogle Scholar
  40. Liu D, Stowie A, de Zavalia N, Leise T, Pathak SS, Drewes LR, Davidson AJ, Amir S, Sonenberg N, Cao R (2018) mTOR signaling in VIP neurons regulates circadian clock synchrony and olfaction. Proc Natl Acad Sci USA 115:E3296–E3304.  https://doi.org/10.1073/pnas.1721578115 CrossRefGoogle Scholar
  41. Loewith R, Hall MN (2011) Target of rapamycin (TOR) in nutrient signaling and growth control. Genetics 189:1177–1201.  https://doi.org/10.1534/genetics.111.133363 CrossRefGoogle Scholar
  42. Mattern DL, Forman LR, Brody S (1982) Circadian rhythms in Neurospora crassa: a mutation affecting temperature compensation. Proc Natl Acad Sci USA 79:825–829.  https://doi.org/10.1073/pnas.79.3.825 CrossRefGoogle Scholar
  43. Mergenhagen D, Schweiger HG (1975) The effect of different inhibitors of transcription and translation on the expression and control of circadian rhythm in individual cells of Acetabularia. Exp Cell Res 94:321–326.  https://doi.org/10.1016/0014-4827(75)90499-1 CrossRefGoogle Scholar
  44. Milev NB, Reddy AB (2015) Circadian redox oscillations and metabolism. Trends Endocrinol Metab 26:430–437.  https://doi.org/10.1016/j.tem.2015.05.012 CrossRefGoogle Scholar
  45. Milev NB, Rhee SG, Reddy AB (2018) Cellular timekeeping: it’s redox o’clock. Cold Spring Harb Perspect Biol.  https://doi.org/10.1101/cshperspect.a027698 Google Scholar
  46. Mills SC, Enganti R, von Arnim AG (2018) What makes ribosomes tick? RNA Biol 15:44–54.  https://doi.org/10.1080/15476286.2017.1391444 CrossRefGoogle Scholar
  47. O’Neill JS, Reddy AB (2011) Circadian clocks in human red blood cells. Nature 469:498–504.  https://doi.org/10.1038/nature09702 CrossRefGoogle Scholar
  48. O’Neill JS, van Ooijen G, Dixon LE, Troein C, Corellou F, Bouget F-Y, Reddy AB, Millar AJ (2011) Circadian rhythms persist without transcription in a eukaryote. Nature 469:554–558.  https://doi.org/10.1038/nature09654 CrossRefGoogle Scholar
  49. Okazaki H, Matsunaga N, Fujioka T, Okazaki F, Akagawa Y, Tsurudome Y, Ono M, Kuwano M, Koyanagi S, Ohdo S (2014) Circadian regulation of mTOR by the ubiquitin pathway in renal cell carcinoma. Cancer Res 74:543–551.  https://doi.org/10.1158/0008-5472.CAN-12-3241 CrossRefGoogle Scholar
  50. Olivares-Yañez C, Emerson J, Kettenbach A, Loros JJ, Dunlap JC, Larrondo LF (2016) Modulation of circadian gene expression and metabolic compensation by the RCO-1 corepressor of Neurospora crassa. Genetics 204:163–176.  https://doi.org/10.1534/genetics.116.191064 CrossRefGoogle Scholar
  51. Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, Schultz PG, Kay SA, Takahashi JS, Hogenesch JB (2002) Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109:307–320.  https://doi.org/10.1016/S0092-8674(02)00722-5 CrossRefGoogle Scholar
  52. Paulose JK, Rucker Iii EB, Cassone VM (2012) Toward the beginning of time: Circadian rhythms in metabolism precede rhythms in clock gene expression in mouse embryonic stem cells. PLoS One 7.  https://doi.org/10.1371/journal.pone.0049555
  53. Putker M, O’Neill JS (2016) Reciprocal control of the circadian clock and cellular redox state—a critical appraisal. Mol Cells 39:6–19.  https://doi.org/10.14348/molcells.2016.2323 CrossRefGoogle Scholar
  54. Putker M, Crosby P, Feeney KA, Hoyle NP, Costa ASH, Gaude E, Frezza C, O’Neill JS (2018) Mammalian circadian period, but not phase and amplitude, is robust against redox and metabolic perturbations. Antioxid Redox Signal 28:507–520.  https://doi.org/10.1089/ars.2016.6911 CrossRefGoogle Scholar
  55. Ramanathan C, Kathale ND, Liu D, Lee C, Freeman DA, Hogenesch JB, Cao R, Liu AC (2018) mTOR signaling regulates central and peripheral circadian clock function. PLoS Genet.  https://doi.org/10.1371/journal.pgen.1007369 Google Scholar
  56. Ramsdale M, Lakin-Thomas PL (2000) sn-1,2-diacylglycerol levels in the fungus Neurospora crassa display circadian rhythmicity. J Biol Chem 275:27541–27550.  https://doi.org/10.1074/jbc.M002911200 Google Scholar
  57. Ratnayake L, Adhvaryu KK, Kafes E, Motavaze K, Lakin-Thomas P (2018) A component of the TOR (target of rapamycin) nutrient-sensing pathway plays a role in circadian rhythmicity in Neurospora crassa. PLoS Genet.  https://doi.org/10.1371/journal.pgen.1007457 Google Scholar
  58. Rey G, Valekunja Utham K, Feeney Kevin A, Wulund L, Milev Nikolay B, Stangherlin A, Ansel-Bollepalli L, Velagapudi V, O’Neill John S, Reddy Akhilesh B (2016) The pentose phosphate pathway regulates the circadian clock. Cell Metab 24:462–473.  https://doi.org/10.1016/j.cmet.2016.07.024 CrossRefGoogle Scholar
  59. Rey G, Milev NB, Valekunja UK, Ch R, Ray S, Silva Dos Santos M, Nagy AD, Antrobus R, MacRae JI, Reddy AB (2018) Metabolic oscillations on the circadian time scale in Drosophila cells lacking clock genes. Mol Syst Biol.  https://doi.org/10.15252/msb.20188376 Google Scholar
  60. Rhoades SD, Nayak K, Zhang SL, Sehgal A, Weljie AM (2018) Circadian- and light-driven metabolic rhythms in Drosophila melanogaster. J Biol Rhythms 33:126–136.  https://doi.org/10.1177/0748730417753003 CrossRefGoogle Scholar
  61. Robles MS, Cox J, Mann M (2014) In-vivo quantitative proteomics reveals a key contribution of post-transcriptional mechanisms to the circadian regulation of liver metabolism. PLoS Genet.  https://doi.org/10.1371/journal.pgen.1004047 Google Scholar
  62. Robles MS, Humphrey SJ, Mann M (2017) Phosphorylation is a central mechanism for circadian control of metabolism and physiology. Cell Metab 25:118–127.  https://doi.org/10.1016/j.cmet.2016.10.004 CrossRefGoogle Scholar
  63. Roenneberg T, Merrow M (1999) Circadian systems and metabolism. J Biol Rhythms 14:449–459.  https://doi.org/10.1073/pnas.0501884102 CrossRefGoogle Scholar
  64. Roenneberg T, Dragovic Z, Merrow M (2005) Demasking biological oscillators: properties and principles of entrainment exemplified by the Neurospora circadian clock. Proc Natl Acad Sci USA 102:7742–7747.  https://doi.org/10.1073/pnas.0501884102 CrossRefGoogle Scholar
  65. Roy S, Beauchemin M, Dagenais-Bellefeuille S, Letourneau L, Cappadocia M, Morse D (2014) The Lingulodinium circadian system lacks rhythmic changes in transcript abundance. BMC Biol.  https://doi.org/10.1186/s12915-014-0107-z Google Scholar
  66. Sahar S, Nin V, Barbosa MT, Chini EN, Sassone-Corsi P (2011) Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation. Aging (Milano) 3:794–802.  https://doi.org/10.18632/aging.100368 CrossRefGoogle Scholar
  67. Sancar G, Brunner M (2014) Circadian clocks and energy metabolism. Cell Mol Life Sci 71:2667–2680.  https://doi.org/10.1007/s00018-014-1574-7 CrossRefGoogle Scholar
  68. Sancar G, Sancar C, Brunner M (2012) Metabolic compensation of the Neurospora clock by a glucose-dependent feedback of the circadian repressor CSP1 on the core oscillator. Genes Dev 26:2435–2442.  https://doi.org/10.1101/gad.199547.112 CrossRefGoogle Scholar
  69. Sancar C, Sancar G, Ha N, Cesbron F, Brunner M (2015) Dawn- and dusk-phased circadian transcription rhythms coordinate anabolic and catabolic functions in Neurospora. BMC Biol.  https://doi.org/10.1186/s12915-015-0126-4 Google Scholar
  70. Shi M, Larrondo LF, Loros JJ, Dunlap JC (2007) A developmental cycle masks output from the circadian oscillator under conditions of choline deficiency in Neurospora. Proc Natl Acad Sci USA 104:20102–20107.  https://doi.org/10.1073/pnas.0706631104 CrossRefGoogle Scholar
  71. Shimobayashi M, Hall MN (2014) Making new contacts: The mTOR network in metabolism and signalling crosstalk. Nat Rev Mol Cell Biol 15:155–162.  https://doi.org/10.1038/nrm3757 CrossRefGoogle Scholar
  72. Storch KF, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, Weitz CJ (2002) Extensive and divergent circadian gene expression in liver and heart. Nature 417:78–83.  https://doi.org/10.1038/nature744 CrossRefGoogle Scholar
  73. Tamaru T, Hattori M, Ninomiya Y, Kawamura G, Varès G, Honda K, Mishra DP, Wang B, Benjamin I, Sassone-Corsi P, Ozawa T, Takamatsu K (2013) ROS stress resets circadian clocks to coordinate pro-survival signals. PLoS One.  https://doi.org/10.1371/journal.pone.0082006 Google Scholar
  74. The Nobel Prize in Physiology or Medicine (Nobel Media AB 2014) (2017) http://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/. Accessed 9 Aug 2018
  75. Tseng R, Goularte NF, Chavan A, Luu J, Cohen SE, Chang YG, Heisler J, Li S, Michael AK, Tripathi S, Golden SS, LiWang A, Partch CL (2017) Structural basis of the day-night transition in a bacterial circadian clock. Science 355:1174–1180.  https://doi.org/10.1126/science.aag2516 CrossRefGoogle Scholar
  76. Tu BP (2010) Ultradian metabolic cycles in yeast. Methods Enzymol 470:857–866.  https://doi.org/10.1016/S0076-6879(10)70035-5 CrossRefGoogle Scholar
  77. van Ooijen G, Millar AJ (2012) Non-transcriptional oscillators in circadian timekeeping. Trends Biochem Sci 37:484–492.  https://doi.org/10.1016/j.tibs.2012.07.006 CrossRefGoogle Scholar
  78. Walton ZE, Patel CH, Brooks RC, Yu Y, Ibrahim-Hashim A, Riddle M, Porcu A, Jiang T, Ecker BL, Tameire F, Koumenis C, Weeraratna AT, Welsh DK, Gillies R, Alwine JC, Zhang L, Powell JD, Dang CV (2018) Acid suspends the circadian clock in hypoxia through inhibition of mTOR. Cell 174:72–87.  https://doi.org/10.1016/j.cell.2018.05.009 CrossRefGoogle Scholar
  79. Woolum JC (1991) A re-examination of the role of the nucleus in generating the circadian rhythm in Acetabularia. J Biol Rhythms 6:129–136.  https://doi.org/10.1177/074873049100600203 CrossRefGoogle Scholar
  80. Wu D (2018) Studies on the function of the prd-1 gene in Neurospora crassa. MSc thesis, Department of Biology, York UniversityGoogle Scholar
  81. Yoshida Y, Iigusa H, Wang N, Hasunuma K (2011) Cross-talk between the cellular redox state and the circadian system in Neurospora. PLoS One.  https://doi.org/10.1371/journal.pone.0028227 Google Scholar
  82. Zhang R, Lahens NF, Ballance HI, Hughes ME, Hogenesch JB (2014) A circadian gene expression atlas in mammals: Implications for biology and medicine. Proc Natl Acad Sci USA 111:16219–16224.  https://doi.org/10.1073/pnas.1408886111 CrossRefGoogle Scholar
  83. Zhang Y, Giacchetti S, Parouchev A, Hadadi E, Li X, Dallmann R, Xandri-Monje H, Portier L, Adam R, Lévi F, Dulong S, Chang Y (2018) Dosing time dependent in vitro pharmacodynamics of Everolimus despite a defective circadian clock. Cell Cycle 17:33–42.  https://doi.org/10.1080/15384101.2017.1387695 CrossRefGoogle Scholar
  84. Zheng X, Sehgal A (2010) AKT and TOR signaling set the pace of the circadian pacemaker. Curr Biol 20:1203–1208.  https://doi.org/10.1016/j.cub.2010.05.027 CrossRefGoogle Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiologyYork UniversityTorontoCanada

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