Anoxia-Reoxygenation Regulates Mitochondrial Dynamics through the Hypoxia Response Pathway, SKN-1/Nrf, and Stomatin-Like Protein STL-1/SLP-2

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Many aerobic organisms encounter oxygen-deprived environments and thus must have adaptive mechanisms to survive such stress. It is important to understand how mitochondria respond to oxygen deprivation given the critical role they play in using oxygen to generate cellular energy. Here we examine mitochondrial stress response in C. elegans, which adapt to extreme oxygen deprivation (anoxia, less than 0.1% oxygen) by entering into a reversible suspended animation state of locomotory arrest. We show that neuronal mitochondria undergo DRP-1-dependent fission in response to anoxia and undergo refusion upon reoxygenation. The hypoxia response pathway, including EGL-9 and HIF-1, is not required for anoxia-induced fission, but does regulate mitochondrial reconstitution during reoxygenation. Mutants for egl-9 exhibit a rapid refusion of mitochondria and a rapid behavioral recovery from suspended animation during reoxygenation; both phenotypes require HIF-1. Mitochondria are significantly larger in egl-9 mutants after reoxygenation, a phenotype similar to stress-induced mitochondria hyperfusion (SIMH). Anoxia results in mitochondrial oxidative stress, and the oxidative response factor SKN-1/Nrf is required for both rapid mitochondrial refusion and rapid behavioral recovery during reoxygenation. In response to anoxia, SKN-1 promotes the expression of the mitochondrial resident protein Stomatin-like 1 (STL-1), which helps facilitate mitochondrial dynamics following anoxia. Our results suggest the existence of a conserved anoxic stress response involving changes in mitochondrial fission and fusion.

Vyšlo v časopise: Anoxia-Reoxygenation Regulates Mitochondrial Dynamics through the Hypoxia Response Pathway, SKN-1/Nrf, and Stomatin-Like Protein STL-1/SLP-2. PLoS Genet 9(12): e32767. doi:10.1371/journal.pgen.1004063
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004063

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1. ZivkovicG, BuckLT (2010) Regulation of AMPA receptor currents by mitochondrial ATP-sensitive K+ channels in anoxic turtle neurons. Journal of neurophysiology 104: 1913–1922.

2. PamenterME, ShinDS, CoorayM, BuckLT (2008) Mitochondrial ATP-sensitive K+ channels regulate NMDAR activity in the cortex of the anoxic western painted turtle. The Journal of physiology 586: 1043–1058.

3. ShinDS, BuckLT (2003) Effect of anoxia and pharmacological anoxia on whole-cell NMDA receptor currents in cortical neurons from the western painted turtle. Physiological and biochemical zoology : PBZ 76: 41–51.

4. ZhuCD, WangZH, YanB (2013) Strategies for hypoxia adaptation in fish species: a review. Journal of comparative physiology B, Biochemical, systemic, and environmental physiology 183: 1005–1013.

5. ZepedaAB, PessoaAJr, CastilloRL, FigueroaCA, PulgarVM, et al. (2013) Cellular and molecular mechanisms in the hypoxic tissue: role of HIF-1 and ROS. Cell biochemistry and function 31: 451–9.

6. CorcoranA, O'ConnorJJ (2013) Hypoxia-inducible factor signalling mechanisms in the central nervous system. Acta physiologica 208: 298–310.

7. MarcouxFW, MorawetzRB, CrowellRM, DeGirolamiU, HalseyJHJr (1982) Differential regional vulnerability in transient focal cerebral ischemia. Stroke; a journal of cerebral circulation 13: 339–346.

8. LiuF, McCulloughLD (2012) Interactions between age, sex, and hormones in experimental ischemic stroke. Neurochem Int 61: 1255–1265.

9. AbeK, AokiM, KawagoeJ, YoshidaT, HattoriA, et al. (1995) Ischemic delayed neuronal death. A mitochondrial hypothesis. Stroke; a journal of cerebral circulation 26: 1478–1489.

10. SinghRP, FrankeK, WielockxB (2012) Hypoxia-mediated regulation of stem cell fate. High altitude medicine & biology 13: 162–168.

11. KimY, LinQ, GlazerPM, YunZ (2009) Hypoxic tumor microenvironment and cancer cell differentiation. Current molecular medicine 9: 425–434.

12. Sen BanerjeeS, ThirunavukkarasuM, Tipu RishiM, SanchezJA, MaulikN, et al. (2012) HIF-prolyl hydroxylases and cardiovascular diseases. Toxicology mechanisms and methods 22: 347–358.

13. GoswamiSK, DasDK (2010) Oxygen Sensing, Cardiac Ischemia, HIF-1alpha and Some Emerging Concepts. Current cardiology reviews 6: 265–273.

14. EltzschigHK, EckleT (2011) Ischemia and reperfusion–from mechanism to translation. Nature medicine 17: 1391–1401.

15. LemastersJJ, TheruvathTP, ZhongZ, NieminenAL (2009) Mitochondrial calcium and the permeability transition in cell death. Biochim Biophys Acta 1787: 1395–1401.

16. MurphyE, SteenbergenC (2008) Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiological reviews 88: 581–609.

17. BrookesPS, YoonY, RobothamJL, AndersMW, SheuSS (2004) Calcium, ATP, and ROS: a mitochondrial love-hate triangle. American journal of physiology Cell physiology 287: C817–833.

18. ShuttTE, McBrideHM (2013) Staying cool in difficult times: mitochondrial dynamics, quality control and the stress response. Biochim Biophys Acta 1833: 417–424.

19. LiuX, HajnoczkyG (2011) Altered fusion dynamics underlie unique morphological changes in mitochondria during hypoxia-reoxygenation stress. Cell death and differentiation 18: 1561–1572.

20. TonderaD, GrandemangeS, JourdainA, KarbowskiM, MattenbergerY, et al. (2009) SLP-2 is required for stress-induced mitochondrial hyperfusion. EMBO J 28: 1589–1600.

21. ItohK, NakamuraK, IijimaM, SesakiH (2013) Mitochondrial dynamics in neurodegeneration. Trends Cell Biol 23: 64–71.

22. DuBoffB, FeanyM, GotzJ (2013) Why size matters - balancing mitochondrial dynamics in Alzheimer's disease. Trends Neurosci 36: 325–335.

23. AndersonGL, DusenberyDB (1977) Critical-Oxygen Tension of Caenorhabdiltis elegans. J Nematol 9: 253–254.

24. Van VoorhiesWA, WardS (2000) Broad oxygen tolerance in the nematode Caenorhabditis elegans. J Exp Biol 203: 2467–2478.

25. Powell-CoffmanJA (2010) Hypoxia signaling and resistance in C. elegans. Trends in endocrinology and metabolism: TEM 21: 435–440.

26. PocockR, HobertO (2008) Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Nat Neurosci 11: 894–900.

27. ChangAJ, BargmannCI (2008) Hypoxia and the HIF-1 transcriptional pathway reorganize a neuronal circuit for oxygen-dependent behavior in Caenorhabditis elegans. Proc Natl Acad Sci U S A 105: 7321–7326.

28. CheungBH, CohenM, RogersC, AlbayramO, de BonoM (2005) Experience-dependent modulation of C. elegans behavior by ambient oxygen. Curr Biol 15: 905–917.

29. MaDK, VozdekR, BhatlaN, HorvitzHR (2012) CYSL-1 interacts with the O2-sensing hydroxylase EGL-9 to promote H2S-modulated hypoxia-induced behavioral plasticity in C. elegans. Neuron 73: 925–940.

30. ParkEC, GhoseP, ShaoZ, YeQ, KangL, et al. (2012) Hypoxia regulates glutamate receptor trafficking through an HIF-independent mechanism. EMBO J 31: 1379–1393.

31. PadillaPA, LadageML (2012) Suspended animation, diapause and quiescence: arresting the cell cycle in C. elegans. Cell cycle 11: 1672–1679.

32. MendenhallAR, LaRueB, PadillaPA (2006) Glyceraldehyde-3-phosphate dehydrogenase mediates anoxia response and survival in Caenorhabditis elegans. Genetics 174: 1173–1187.

33. MendenhallAR, LeBlancMG, MohanDP, PadillaPA (2009) Reduction in ovulation or male sex phenotype increases long-term anoxia survival in a daf-16-independent manner in Caenorhabditis elegans. Physiological genomics 36: 167–178.

34. MillerDL, RothMB (2009) C. elegans are protected from lethal hypoxia by an embryonic diapause. Current biology : CB 19: 1233–1237.

35. FongGH, TakedaK (2008) Role and regulation of prolyl hydroxylase domain proteins. Cell Death Differ 15: 635–641.

36. AragonesJ, FraislP, BaesM, CarmelietP (2009) Oxygen sensors at the crossroad of metabolism. Cell Metab 9: 11–22.

37. EpsteinAC, GleadleJM, McNeillLA, HewitsonKS, O'RourkeJ, et al. (2001) C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107: 43–54.

38. BruickRK, McKnightSL (2001) A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294: 1337–1340.

39. SemenzaGL (2009) Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda) 24: 97–106.

40. FandreyJ, GassmannM (2009) Oxygen sensing and the activation of the hypoxia inducible factor 1 (HIF-1)–invited article. Adv Exp Med Biol 648: 197–206.

41. HayakawaT, KatoK, HayakawaR, HisamotoN, MatsumotoK, et al. (2011) Regulation of anoxic death in Caenorhabditis elegans by mammalian apoptosis signal-regulating kinase (ASK) family proteins. Genetics 187: 785–792.

42. ScottBA, AvidanMS, CrowderCM (2002) Regulation of hypoxic death in C. elegans by the insulin/IGF receptor homolog DAF-2. Science 296: 2388–2391.

43. LaRueBL, PadillaPA (2011) Environmental and genetic preconditioning for long-term anoxia responses requires AMPK in Caenorhabditis elegans. PloS one 6: e16790.

44. PadillaPA, NystulTG, ZagerRA, JohnsonAC, RothMB (2002) Dephosphorylation of cell cycle-regulated proteins correlates with anoxia-induced suspended animation in Caenorhabditis elegans. Mol Biol Cell 13: 1473–1483.

45. NunnariJ, SuomalainenA (2012) Mitochondria: in sickness and in health. Cell 148: 1145–1159.

46. DarbyC, CosmaCL, ThomasJH, ManoilC (1999) Lethal paralysis of Caenorhabditis elegans by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 96: 15202–15207.

47. JiangH, GuoR, Powell-CoffmanJA (2001) The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia. Proc Natl Acad Sci U S A 98: 7916–7921.

48. ShenC, ShaoZ, Powell-CoffmanJA (2006) The Caenorhabditis elegans rhy-1 gene inhibits HIF-1 hypoxia-inducible factor activity in a negative feedback loop that does not include vhl-1. Genetics 174: 1205–1214.

49. ShaoZ, ZhangY, YeQ, SaldanhaJN, Powell-CoffmanJA (2010) C. elegans SWAN-1 Binds to EGL-9 and regulates HIF-1-mediated resistance to the bacterial pathogen Pseudomonas aeruginosa PAO1. PLoS Pathog 6: e1001075.

50. WiedemannN, StillerSB, PfannerN (2013) Activation and degradation of mitofusins: two pathways regulate mitochondrial fusion by reversible ubiquitylation. Mol Cell 49: 423–425.

51. PonLA (2013) Mitochondrial fission: rings around the organelle. Current biology : CB 23: R279–281.

52. OteraH, IshiharaN, MiharaK (2013) New insights into the function and regulation of mitochondrial fission. Biochim Biophys Acta 1833: 1256–1268.

53. HansonGT, AggelerR, OglesbeeD, CannonM, CapaldiRA, et al. (2004) Investigating mitochondrial redox potential with redox-sensitive green fluorescent protein indicators. J Biol Chem 279: 13044–13053.

54. CannonMB, RemingtonSJ (2008) Redox-sensitive green fluorescent protein: probes for dynamic intracellular redox responses. A review. Methods in molecular biology 476: 51–65.

55. AnJH, BlackwellTK (2003) SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev 17: 1882–1893.

56. PaekJ, LoJY, NarasimhanSD, NguyenTN, Glover-CutterK, et al. (2012) Mitochondrial SKN-1/Nrf mediates a conserved starvation response. Cell metabolism 16: 526–537.

57. InoueH, HisamotoN, AnJH, OliveiraRP, NishidaE, et al. (2005) The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Genes Dev 19: 2278–2283.

58. OliveiraRP, Porter AbateJ, DilksK, LandisJ, AshrafJ, et al. (2009) Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Aging cell 8: 524–541.

59. NiuW, LuZJ, ZhongM, SarovM, MurrayJI, et al. (2011) Diverse transcription factor binding features revealed by genome-wide ChIP-seq in C. elegans. Genome Res 21: 245–254.

60. WangY, MorrowJS (2000) Identification and characterization of human SLP-2, a novel homologue of stomatin (band 7.2b) present in erythrocytes and other tissues. J Biol Chem 275: 8062–8071.

61. TavernarakisN, DriscollM, KyrpidesNC (1999) The SPFH domain: implicated in regulating targeted protein turnover in stomatins and other membrane-associated proteins. Trends in biochemical sciences 24: 425–427.

62. IchishitaR, TanakaK, SugiuraY, SayanoT, MiharaK, et al. (2008) An RNAi screen for mitochondrial proteins required to maintain the morphology of the organelle in Caenorhabditis elegans. Journal of biochemistry 143: 449–454.

63. GandreS, van der BliekAM (2007) Mitochondrial division in Caenorhabditis elegans. Methods in molecular biology 372: 485–501.

64. CochemeHM, MurphyMP (2008) Complex I is the major site of mitochondrial superoxide production by paraquat. J Biol Chem 283: 1786–1798.

65. TavernarakisN, WangSL, DorovkovM, RyazanovA, DriscollM (2000) Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes. Nat Genet 24: 180–183.

66. ShenC, NettletonD, JiangM, KimSK, Powell-CoffmanJA (2005) Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in Caenorhabditis elegans. J Biol Chem 280: 20580–20588.

67. ShaoZ, ZhangY, Powell-CoffmanJA (2009) Two distinct roles for EGL-9 in the regulation of HIF-1-mediated gene expression in Caenorhabditis elegans. Genetics 183: 821–829.

68. GrayJM, KarowDS, LuH, ChangAJ, ChangJS, et al. (2004) Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature 430: 317–322.

69. BranickyRS, SchaferWR (2008) Oxygen homeostasis: how the worm adapts to variable oxygen levels. Curr Biol 18: R559–560.

70. Van VoorhiesWA, WardS (1999) Genetic and environmental conditions that increase longevity in Caenorhabditis elegans decrease metabolic rate. Proc Natl Acad Sci U S A 96: 11399–11403.

71. HajekP, ChomynA, AttardiG (2007) Identification of a novel mitochondrial complex containing mitofusin 2 and stomatin-like protein 2. J Biol Chem 282: 5670–5681.

72. ChristieDA, LemkeCD, EliasIM, ChauLA, KirchhofMG, et al. (2011) Stomatin-like protein 2 binds cardiolipin and regulates mitochondrial biogenesis and function. Mol Cell Biol 31: 3845–3856.

73. HackenbrockCR (1966) Ultrastructural bases for metabolically linked mechanical activity in mitochondria. I. Reversible ultrastructural changes with change in metabolic steady state in isolated liver mitochondria. J Cell Biol 30: 269–297.

74. RollandSG, MotoriE, MemarN, HenchJ, FrankS, et al. (2013) Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion. Proceedings of the National Academy of Sciences of the United States of America 110: E2967–2976.

75. RossignolR, GilkersonR, AggelerR, YamagataK, RemingtonSJ, et al. (2004) Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer research 64: 985–993.

76. ParonePA, Da CruzS, TonderaD, MattenbergerY, JamesDI, et al. (2008) Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA. PloS one 3: e3257.

77. TwigG, ElorzaA, MolinaAJ, MohamedH, WikstromJD, et al. (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27: 433–446.

78. EspositoG, Di SchiaviE, BergamascoC, BazzicalupoP (2007) Efficient and cell specific knock-down of gene function in targeted C. elegans neurons. Gene 395: 170–176.

79. CollinsTJ (2007) ImageJ for microscopy. Biotechniques 43: 25–30.