リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Diverse reaction behaviors of artificial ubiquinones in mitochondrial respiratory complex I」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
リケラボ

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Diverse reaction behaviors of artificial ubiquinones in mitochondrial respiratory complex I

Uno, Shinpei Masuya, Takahiro Zdorevskyi, Oleksii Ikunishi, Ryou Shinzawa-Itoh, Kyoko Lasham, Jonathan Sharma, Vivek Murai, Masatoshi Miyoshi, Hideto 京都大学 DOI:10.1016/j.jbc.2022.102075

2022.07

概要

The ubiquinone (UQ) reduction step catalyzed by NADH-UQ oxidoreductase (mitochondrial respiratory complex I) is key to triggering proton translocation across the inner mitochondrial membrane. Structural studies have identified a long, narrow, UQ-accessing tunnel within the enzyme. We previously demonstrated that synthetic oversized UQs, which are unlikely to transit this narrow tunnel, are catalytically reduced by native complex I embedded in submitochondrial particles but not by the isolated enzyme. To explain this contradiction, we hypothesized that access of oversized UQs to the reaction site is obstructed in the isolated enzyme because their access route is altered following detergent solubilization from the inner mitochondrial membrane. In the present study, we investigated this using two pairs of photoreactive UQs (pUQm-₁/pUQp-₁ and pUQm-₂/pUQp-₂), with each pair having the same chemical properties except for a ∼1.0 Å difference in side-chain widths. Despite this subtle difference, reduction of the wider pUQs by the isolated complex was significantly slower than of the narrower pUQs, but both were similarly reduced by the native enzyme. In addition, photoaffinity-labeling experiments using the four [¹²⁵I]pUQs demonstrated that their side chains predominantly label the ND1 subunit with both enzymes but at different regions around the tunnel. Finally, we show that the suppressive effects of different types of inhibitors on the labeling significantly changed depending on [¹²⁵I]pUQs used, indicating that [¹²⁵I]pUQs and these inhibitors do not necessarily share a common binding cavity. Altogether, we conclude that the reaction behaviors of pUQs cannot be simply explained by the canonical UQ tunnel model.

論文の公開元へ

この論文で使われている画像

関連論文

関連論文をもっと見る

参考文献

1. Hirst, J. (2013) Mitochondrial complex I. Annu. Rev. Biochem. 82, 551–575

2. Sazanov, L. A. (2015) A giant molecular proton pump: structure and mechanism of respiratory complex I. Nat. Mol. Cell Biol. 16, 375–388

3. Wirth, C., Brandt, U., Hunte, C., and Zickermann, V. (2016) Structure and function of mitochondrial complex I. Biochim. Biophys. Acta 1857, 902–914

4. Wong, H.-S., Dighe, P. A., Mezera, V., Monternier, P.-A., and Brand, M. D. (2017) Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J. Biol. Chem. 292, 16804–16809

5. Zhu, J., Vinothkumar, K. R., and Hirst, J. (2016) Structure of mammalian respiratory complex I. Nature 536, 354–358

6. Blaza, J. N., Vinothkumar, K. R., and Hirst, J. (2018) Structure of the deactive state of mammalian respiratory complex I. Structure 26, 312–319

7. Fiedorczuk, K., Letts, J. A., Degliesposti, G., Kaszuba, K., Skehel, M., and Sazanov, L. A. (2016) Atomic structure of the entire mammalian mitochondrial complex I. Nature 538, 406–410

8. Wu, M., Gu, J., Guo, R., Huang, Y., and Yang, M. (2016) Structure of mammalian respiratory supercomplex I1III2IV1. Cell 167, 1598–1609

9. Agip, A.-N. A., Blaza, J. N., Gridges, H. R., Viscomi, C., Rawson, S., Muench, S. P., et al. (2018) Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states. Nat. Struct. Mol. Biol. 25, 548–556

10. Guo, R., Zong, S., Wu, M., Gu, J., and Yang, M. (2017) Architecture of human mitochondrial respiratory megacomplex I2III2IV2. Cell 170, 1247–1257

11. Parey, K., Haapanen, O., Sharma, V., Köfeler, H., Züllig, T., Prinz, S., et al. (2019) High-resolution cryo-EM structures of respiratory complex I: mechanism, assembly, and disease. Sci. Adv. 5, eaax9484

12. Grba, D. N., and Hirst, J. (2020) Mitochondrial complex I structure reveals ordered water moleculaes for catalysis and proton translocation. Nat. Struct. Mol. Biol. 27, 892–900

13. Bridges, H. R., Fedor, J. G., Blaza, J. N., Lica, A. D., Jussupow, A., Jarman, O. D., et al. (2020) Structure of inhibitor-bound mammalian complex I. Nat. Commun. 11, 5261

14. Kampjut, D., and Sazanov, L. A. (2020) The coupling mechanism of mammalian respiratory complex I. Science 370, eabc4209

15. Parey, K., Lasham, J., Mills, D. J., Djurabekova, A., Haapanen, O., Yoga, E. G., et al. (2021) High-resolution structure and dynamics of mitochondrial complex I-insights into the proton pumping mechanism. Sci. Adv. 7, eabj3221

16. Sharma, V., Belevich, G., Gamiz-Hernandez, A. P., Róg, T., Vattulainen, I., Verkhovskaya, M. L., et al. (2015) Redox-induced activation of the proton pump in the respiratory complex I. Proc. Natl. Acad. Sci. U. S. A. 122, 11571–11576

17. Luca, A. D., Gamiz-Hernandez, A. P., and Kaila, V. R. I. (2017) Symmetryrelated proton transfer pathways in respiratory complex I. Proc. Natl. Acad. Sci. U. S. A. 114, 6314–6321

18. Gamiz-Hernandez, A. P., Jussupow, A., Johansson, M. P., and Kaila, V. R. I. (2017) Terminal electron-proton transfer dynamics in the quinone reduction of respiratory complex I. J. Am. Chem. Soc. 139, 16282–16288

19. Djurabekova, A., Haapanen, O., and Sharma, V. (2020) Proton motive function of the terminal antiporter-like subunit in respiratory complex I. Biochim. Biophys. Acta Bioenerg. 1861, 148185

20. Haapanen, O., and Sharma, V. (2021) Redox- and protonation-state driven substrate-protein dynamics in respiratory complex I. Curr. Opin. Electrochem. 29, 100741

21. Baradaran, R., Berrisford, J. M., Minhas, G. S., and Sazanov, L. A. (2013) Crystal structure of the entire respiratory complex I. Nature 494, 443–448

22. Zickermann, V., Wirth, C., Nasiri, H., Siegmund, K., Schwalbe, H., Hunte, C., et al. (2015) Mechanistic insight from the crystal structure of mitochondrial complex I. Science 347, 44–49

23. Fedor, J. G., Jones, A. J. Y., Di Luca, A., Kaila, V. R. I., and Hirst, J. (2017) Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I. Proc. Natl. Acad. Sci. U. S. A. 114, 12737–12742

24. Yoga, E. G., Parey, K., Djurabekova, A., Haapanen, O., Siegmund, K., Zwicker, K., et al. (2020) Essential role of accessory subunit LYRM6 in the mechanism of mitochondrial complex I. Nat. Commun. 11, 6008

25. Uno, S., Kimura, H., Murai, M., and Miyoshi, H. (2019) Exploring the quinone/inhibitor-binding pocket in mitochondrial respiratory complex I by chemical biology approaches. J. Biol. Chem. 294, 679–696

26. Banba, A., Tsuji, A., Kimura, H., Murai, M., and Miyoshi, H. (2019) Defining the mechanism of action of S1QELs, specific suppressors of superoxide production in the quinone-reaction site in mitochondrial complex I. J. Biol. Chem. 294, 6550–6561

27. Uno, S., Masuya, T., Shinzawa-Itoh, K., Lasham, J., Haapanen, O., Shiba, T., et al. (2020) Oversized ubiquinones as molecular probes for structural dynamics of the ubiquinone reaction site in mitochondrial respiratory complex I. J. Biol. Chem. 295, 2449–2463

28. Tsuji, A., Akao, T., Masuya, T., Murai, M., and Miyoshi, H. (2020) IACS010759, a potent inhibitor of glycolysis-deficient hypoxic tumor cells, inhibits mitochondrial respiratory complex I through a unique mechanism. J. Biol. Chem. 295, 7481–7491

29. Masuya, T., Uno, S., Murai, M., and Miyoshi, H. (2021) Pinpoint dual chemical cross-linking explores structural dynamics of the ubiquinone reaction site in mitochondrial complex I. Biochemistry 60, 813–824

30. Haapanen, O., Djurabekova, A., and Sharma, V. (2019) Role of second quinone binding site in proton pumping by respiratory complex I. Front. Chem. 7, 221

31. Gu, J., Liu, T., Guo, R., Zhang, L., and Yang, M. (2022) The coupling mechanism of mammalian mitochondrial complex I. Nat. Struct. Mol. Biol. 29, 172–182

32. Warnau, J., Sharma, V., Gamiz-Hernandez, A. P., Luca, A. D., Outi Haapanen, O., Vattulainen, I., et al. (2018) Redox-coupled quinone dynamics in the respiratory complex I. Proc. Natl. Acad. Sci. U. S. A. 115, E8413–E8420

33. Teixeira, M. H., and Arantes, G. M. (2019) Balanced internal hydration discriminates substrate binding to respiratory complex I. Biochim. Biophys. Acta Bioenerg. 1960, 541–548

34. Grivennikova, V. G., Kapustin, A. N., and Vinogradov, A. D. (2001) Catalytic activity of NADH-ubiquinone oxidoreductase (complex I) in intact mitochondria: evidence for the slow active/inactive transition. J. Biol. Chem. 276, 9038–9044

35. Galkin, A., Meyer, B., Wittig, I., Kara, M., Schägger, H., Vinogradov, A., et al. (2008) Identification of the mitochondrial ND3 subunit as a structural component involved in the active/deactive enzyme transition of respiratory complex I. J. Biol. Chem. 283, 20907–20913

36. Galkin, A., and Moncada, S. (2007) S-Nitrosation of mitochondrial complex I depends on its structural conformation. J. Biol. Chem. 282, 37448–37453

37. Schägger, H. (2006) Tricine-SDS-PAGE. Nat. Protoc. 1, 16–21

38. Murai, M., Mashimo, Y., Hirst, J., and Miyoshi, H. (2011) Exploring interactions between the 49 kDa and ND1 subunits in mitochondrial NADH-ubiquinone oxidoreductase (complex I) by photoaffinity labeling. Biochemistry 50, 6901–6908

39. Kakutani, N., Murai, M., Sakiyama, N., and Miyoshi, H. (2010) Exploring the binding site of Δlac-acetogenin in bovine heart mitochondrial NADH-ubiquinone oxidoreductase. Biochemistry 49, 4794–4803

40. Colombini, M. (2009) The published 3D structure of the VDAC channel: native or not? Trends Biochem. Sci. 34, 382–389

41. Hiller, S., Abramson, J., Mannella, C., Wagner, G., and Zeth, K. (2010) The 3D structures of VDAC represent a native conformation. Trends Biochem. Sci. 35, 514–521

42. Rey, M., Forest, E., and Pelosi, L. (2012) Exploring the conformational dynamics of the bovine ADP/ATP carrier in mitochondria. Biochemistry 51, 9727–9735

43. Crichton, P. G., Lee, Y., Ruprecht, J. J., Cerson, E., Thangaratnarajah, C., King, M. S., et al. (2015) Trends in thermostability provide information on the nature of substrate, inhibitor, and lipid interactions with mitochondrial carriers. J. Biol. Chem. 290, 8206–8217

44. Steuber, J., Vohl, G., Casutt, M. S., Vorburger, T., Diederichs, K., and Fritz, G. (2014) Structure of the V. cholerae Na+-pumping NADH: quinone oxidoreductase. Nature 516, 62–67

45. Ito, T., Murai, M., Ninokura, S., Kitazumi, Y., Mezic, K. G., Cress, B. F., et al. (2017) Identification of the binding sites for ubiquinone and inhibitors in the Na+-pumping NADH-ubiquinone oxidoreductase of Vibrio cholerae by photoaffinity labeling. J. Biol. Chem. 292, 7727–7742

46. Yoga, E. G., Angerer, H., Parey, K., and Zickermann, V. (2020) Respiratory complex I- mechanistic insights and advances in structural determination. Biochim. Biophys. Acta Bioenerg. 1861, 148153

47. Amarneh, B., and Vik, S. B. (2003) Mutagenesis of subunit N of the Escherichia coli complex I. Identification of the initiation codon and the sensitivity of mutants to decylubiquinone. Biochemistry 42, 4800–4808

48. Chung, I., Wright, J. J., Bridges, H. R., Ivanov, B. S., Biner, O., Pereira, C. S., et al. (2022) Cryo-EM structures define ubiquinone-10 binding to mitochondrial complex I and conformational transitions accompanying Q-site occupancy. Nat. Commun. 13, 2758

49. Brand, M. D., Goncalves, R. L. S., Orr, A. L., Vargas, L., Gerencser, A. A., Jensen, M. B., et al. (2016) Suppressors of superoxide-H2O2 production at site IQ of mitochondrial complex I protect against stem cell hyperplasia and ischemia-reperfusion injury. Cell Metab. 24, 582–592

50. Molina, J. R., Sun, Y., Protopopova, M., Gera, S., Bandi, M., Bristow, C., et al. (2018) An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat. Med. 24, 1036–1046

51. Baccelli, I., Gareau, Y., Lehnertz, B., Gingras, S., Spinella, J.-F., Corneau, S., et al. (2019) Mubritinib targets the electron transport chain complex I and reveals the landscape of OXPHOS dependency in acute myeloid leukemia. Cancer Cell 36, 84–99

52. Madhusudhan, N., Hu, B., Mishra, P., Calva-Moreno, J. F., Patel, K., Boriack, R., et al. (2020) Target discovery of selective non-small-cell lung cancer toxins reveals inhibitors of mitochondrial complex I. ACS Chem. Biol. 15, 158–170

53. Rieske, J. S. (1967) Preparation and properties of reduced coenzyme Qcytochrome c reductase (complex III of the respiratory chain). Methods Enzymol. 10, 239–245

54. Matsuno-Yagi, A., and Hatefi, Y. (1985) Studies on the mechanism of oxidative phosphorylation. J. Biol. Chem. 260, 14424–14427

55. Murai, M., Ichimaru, N., Abe, M., Nishioka, T., and Miyoshi, H. (2006) Mode of inhibitory action of Δlac-acetogenins, a new class of inhibitors of bovine heart mitochondrial complex I. Biochemistry 45, 9778–9787

56. Shimada, S., Maeda, S., Hikita, M., Mieda-Higa, K., Uene, S., Nariai, Y., et al. (2018) Solubilization conditions for bovine heart mitochondrial membranes allow selective purification of large quantities of respiratory complexes I, III, and V. Protein Expr. Purif. 150, 33–43

57. Murai, M., and Miyoshi, H. (2019) Photoaffinity labeling of respiratory complex I in bovine heart submitochondrial particles by photoreactive [125I]amilorides. Bio Protoc. 9, e3349

58. Schägger, H., and von Jagow, G. (1991) Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form. Anal. Biochem. 199, 223–231

59. Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685

60. Rais, I., Kara, M., and Schägger, H. (2004) Two-dimensional electrophoresis for the isolation of integral membrane proteins and mass spectrometric identification. Proteomics 4, 2567–2571

61. Cleveland, D. W., Fishcher, M. W., Kirschner, M. W., and Laemmli, U. K. (1977) Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. J. Biol. Chem. 252, 1102–1106

62. Jo, S., Kim, T., Iyer, V. G., and Im, W. (2008) CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859–1865

63. Fiser, A., and Sali, A. (2003) Modeller: generation and refinement of homology-based protein structure models. Methods Enzymol. 374, 461–491

64. Huang, J., and MacKerell, A. D., Jr. (2013) CHARMM36 all-atom additive protein force field: validation based on comparison to NMR data. J. Comp. Chem. 25, 2135–2145

65. Galassi, V. V., and Arantes, G. M. (2015) Partition, orientation and mobility of ubiquinones in a lipid bilayer. Biochim. Biophys. Acta 1847, 1560–1573

66. Chang, C. H., and Kim, K. (2009) Density functional theory calculation of bonding and charge parameters for molecular dynamics studies on [FeFe] hydrogenases. J. Chem. Theory Comput. 5, 1137–1145

67. Kim, S., Lee, J., Jo, S., Brooks, C. L., III, Lee, H. S., and Im, W. (2017) CHARMM-GUI ligand reader and modeler for CHARMM force field generation of small molecules. J. Comput. Chem. 38, 1879–1886

68. Phillips, J. C., Hardy, D. J., Maia, J. D. C., Stone, J. E., Ribeiro, J. V., Rafael, C., et al. (2020) Scalable molecular dynamics on CPU and GPU architectures with NAMD. J. Chem. Phys. 153, 044130

69. Abraham, M. J., Murtola, T., Schulz, R., Páll, S., Smith, J. C., Hess, B., et al. (2015) Gromacs: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1-2, 19–25

70. Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A., and Haak, J. R. (1984) Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81, 3684–3690

71. Nosé, S. (1984) A unified formulation of the constant temperature molecular dynamics methods. J. Chem. Phys. 81, 511–519

72. Hoover, W. G. (1985) Canonical dynamics: equilibrium phase-space distributions. Phys. Rev. A Gen. Phys. 31, 1695–1697

73. Parrinello, M., and Rahman, A. (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J. Appl. Phys. 52, 7182–7190

74. Verlet, L. (1967) Computer ’experiments’ on classical fluids. I. Thermodynamical properties of Lennard-Jones molecules. Phys. Rev. 159, 98–103

75. Darden, T., York, D., and Pedersen, L. (1993) Particle mesh Ewald: an nlog(N) method for Ewald sums in large systems. J. Chem. Phys. 98, 10089–10092

76. Hess, B., Bekker, H., Berendsen, H. J. C., and Fraaije, J. G. E. M. (1997) Lincs: a linear constraint solver for molecular simulations. J. Comp. Chem. 18, 1463–1472

77. Humphrey, W., Dalke, A., and Schulten, K. (1996) VMD - visual molecular dynamics. J. Mol. Graph. 14, 33–38

78. The PyMOL Molecular Graphics System, Version 2.2.3. (2021). Schrödinger, LLC, New York

79. Pravda, L., Sehnal, D., Tousek, D., Navrátilová, V., Bazgier, V., Berka, K., et al. (2018) MOLEonline: a web-based tool for analyzing channels, tunnels and pores. Nucleic Acids Res. 46, W368–W373

80. Lu, X., Cseh, S., Byun, H. S., Tigyi, G., and Bittman, R. (2003) Total synthesis of two photoactivatable analogues of the growth-factor-like mediator sphingosine 1-phosphate: differential interaction with protein targets. J. Org. Chem. 68, 7046–7050

81. Hashimoto, M., Kato, Y., and Hatanaka, Y. (2006) Simple method for the introduction of iodo-label on (3-trifluoromethyl) phenyldiazirine for photoaffinity labeling. Tetrahedron Lett. 47, 3391–3394

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文
を
一発検索！

この論文の関連論文を見る