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Respiratory complex I in mitochondrial membrane catalyzes oversized ubiquinones

Ikunishi, Ryo Otani, Ryohei Masuya, Takahiro Shinzawa-Itoh, Kyoko Shiba, Tomoo Murai, Masatoshi Miyoshi, Hideto 京都大学 DOI:10.1016/j.jbc.2023.105001

2023.08

概要

NADH-ubiquinone (UQ) oxidoreductase (complex I) couples electron transfer from NADH to UQ with proton translocation in its membrane part. The UQ reduction step is key to triggering proton translocation. Structural studies have identified a long, narrow, tunnel-like cavity within complex I, through which UQ may access a deep reaction site. To elucidate the physiological relevance of this UQ-accessing tunnel, we previously investigated whether a series of oversized UQs (OS-UQs), whose tail moiety is too large to enter and transit the narrow tunnel, can be catalytically reduced by complex I using the native enzyme in bovine heart submitochondrial particles (SMPs) and the isolated enzyme reconstituted into liposomes. Nevertheless, the physiological relevance remained unclear because some amphiphilic OS-UQs were reduced in SMPs but not in proteoliposomes, and investigation of extremely hydrophobic OS-UQs was not possible in SMPs. To uniformly assess the electron transfer activities of all OS-UQs with the native complex I, here we present a new assay system using SMPs, which were fused with liposomes incorporating OS-UQ and supplemented with a parasitic quinol oxidase to recycle reduced OS-UQ. In this system, all OS-UQs tested were reduced by the native enzyme, and the reduction was coupled with proton translocation. This finding does not support the canonical tunnel model. We propose that the UQ reaction cavity is flexibly open in the native enzyme to allow OS-UQs to access the reaction site, but their access is obstructed in the isolated enzyme as the cavity is altered by detergent-solubilizing from the mitochondrial membrane.

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参考文献

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

551–575

EDITORS’ PICK: Respiratory complex I catalyzes oversized ubiquinones

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. 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

7. 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. Struc. Mol.

Biol. 25, 548–556

8. Guo, R., Zong, S., Wu, M., Gu, J., and Yang, M. (2017) Architecture of

human mitochondrial respiratory megacomplex I2III2IV2. Cell 170,

1247–1257

9. Grba, D. N., and Hirst, J. (2020) Mitochondrial complex I structure reveals ordered water molecules for catalysis and proton translocation. Nat.

Struc. Mol. Biol. 27, 892–900

10. 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

11. Kampjut, D., and Sazanov, L. A. (2020) The coupling mechanism of

mammalian respiratory complex I. Science 370, eabc4209

12. 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

13. 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

14. Chung, I., Serreli, R., Cross, J. B., Di Francesco, M. E., Marszalek, J. R., and

Hirst, J. (2021) Cork-in-bottle mechanism of inhibitor binding to

mammalian complex I. Sci. Adv. 7, eabg4000

15. Gu, J., Liu, T., Guo, R., Zhang, L., and Yang, M. (2022) The coupling

mechanism of mammalian mitochondrial complex I. Nat. Struc. Mol.

Biol. 29, 172–182

16. 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

17. Bridges, H. R., Blaza, J. N., Yin, Z., Chung, I., Pollak, M. N., and Hirst, J.

(2022) Structural basis of mammalian respiratory complex I inhibition by

medicinal biguanides. Science 379, 351–357

18. 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

19. 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

20. 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

21. 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

22. Haapanen, O., and Sharma, V. (2021) Redox- and protonation-state

driven substrate-protein dynamics in respiratory complex I. Curr. Opin.

Electrochem. 29, 100741

23. 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

24. 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

25. Wikström, M., Sharma, V., Kaila, V. R., Hosler, J. P., and Hummer, G.

(2015) New perspectives on proton pumping in cellular respiration.

Chem. Rev. 115, 2196–2221

26. Wikström, M., Djurabekova, A., and Sharma, V. (2023) On the role of

ubiquinone in the proton translocation mechanism of respiratory complex I. FEBS Lett. 597, 224–236

27. 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

28. 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

29. 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

30. 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

31. 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

32. Uno, S., Masuya, T., Zdorevskyi, O., Ikunishi, R., Shinzawa-Itoh, K.,

Lasham, J., et al. (2022) Diverse reaction behaviors of artificial ubiquinones in mitochondrial respiratory complex I. J. Biol. Chem. 298, 102075

33. Jones, A. J. Y., Blaza, J. N., Bridges, H. R., May, B., Moore, A. L., and

Hirst, J. (2016) A self-assembled respiratory chain that catalyzes NADH

oxidation by ubiquinone-10 cycling between complex I and the alternative oxidase. Angew. Chem. Int. Ed. 55, 728–731

34. Huang, L. S., Cobessi, D., Tung, E. Y., and Berry, E. A. (2005) Binding of

the respiratory chain inhibitor antimycin to the mitochondrial bc1

complex: a new crystal structure reveals an altered intramolecular

hydrogen-bonding pattern. J. Mol. Biol. 351, 573–597

35. Colombini, M. (2009) The published 3D structure of the VDAC channel:

native or not? Trends Biochem. Sci. 34, 382–389

36. 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

37. Rey, M., Forest, E., and Pelosi, L. (2012) Exploring the conformational

dynamics of the bovine ADP/ATP carrier in mitochondria. Biochemistry

51, 9727–9735

38. 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

39. Kishikawa, J., Ishikawa, M., Masuya, Y., Murai, M., Kitazumi, Y., Butler,

N. L., et al. (2022) Cryo-EM structures of Na+-pumping NADHubiquinone oxidoreductase from Vibrio cholerae. Nat. Commun. 13, 4082

40. Schneider, H., Lemasters, J. J., and Hackenbrock, C. R. (1982) Lateral

diffusion of ubiquinone during electron transfer in phospholipid- and

ubiquinone-enriched mitochondrial membranes. J. Biol. Chem. 257,

10789–10793

41. Fedor, J. G., and Hirst, J. (2018) Mitochondrial supercomplexes do not

enhance catalysis by quinone channeling. Cell Metab. 28, 525–531

42. Shiba, T., Kido, Y., Sakamoto, K., Inaokaa, D. K., Tsuge, C., Ryoko Tatsumi, R., et al. (2013) Structure of the trypanosome cyanide-insensitive

alternative oxidase. Proc. Natl. Acad. Sci. U. S. A. 110, 4580–4585

J. Biol. Chem. (2023) 299(8) 105001

11

EDITORS’ PICK: Respiratory complex I catalyzes oversized ubiquinones

43. Kröger, A., and Klingenberg, M. (1973) Further evidence for the pool

function of ubiquinone as derived from the inhibition of the electron

transport by antimycin. Eur. J. Biochem. 39, 313–323

44. Shiba, T., Inaoka, D. K., Takahashi, G., Tsuge, C., Kido, Y., Young, L.,

et al. (2019) Insights into the ubiquinol/dioxygen binding and proton

relay pathways of the alternative oxidase. Biochim. Biophys. Acta 1860,

375–382

45. 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

46. 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

47. 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

48. 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

49. 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

50. Xu, Y., Xue, D., Bankhead, A., and Neamati, N. (2020) Why all the fuss

about oxidative phosphorylation (OXPHOS)? J. Med. Chem. 63,

14276–14307

51. Yap, T. A., Daver, N., Mahendra, M., Zhang, J., Kamiya-Matsuoka, C.,

Meric-Bernstam, F., et al. (2023) Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase

I trials. Nat. Med. 29, 115–126

52. 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

53. Wong, H. S., Monternier, P. A., and Brand, M. D. (2019) S1QELs suppress mitochondrial superoxide/hydrogen peroxide production from site

IQ without inhibiting reverse electron flow through complex I. Free Radic.

Biol. Med. 143, 545–559

54. Matsuno-Yagi, A., and Hatefi, Y. (1985) Studies on the mechanism of

oxidative phosphorylation. J. Biol. Chem. 260, 11424–11427

55. Shimada, S., Maeda, S., Hikita, M., Maeda-Hikita, 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. Prot. Expr. Pur. 150, 33–43

56. Kido, K., Sakamoto, K., Nakamura, K., Harada, M., Suzuk, T., Yabu, Y.,

et al. (2010) Purification and kinetic characterization of recombinant

alternative oxidase from Trypanosoma brucei brucei. Biochim. Biophys.

Acta 1797, 443–450

57. Shintou, K., Nakano, M., Kamo, T., Kuroda, Y., and Handa, T. (2007)

Interaction of an amphipathic peptide with phosphatidylcholine/phosphatidylethanolamine mixed membrane. Biophys. J. 93, 3900–3906

58. Abe, M., Hasegawa, Y., Oku, M., Sawada, Y., Tanaka, E., Sakai, Y., et al.

(2016) Mechanism for remodeling of the acyl chain composition of cardiolipin catalyzed by Saccharomyces cerevisiae tafazzin. J. Biol. Chem. 291,

15491–15502

59. Krämer, R. (1982) Cholesterol as activator of ADP-ATP exchange in

reconstituted liposomes and in mitochondria. Biochim. Biophys. Acta

693, 296–304

60. Kaplan, R. S., and Pedersen, P. L. (1985) Determination of microgram

quantities of protein in the presence of milligram levels of lipid with

amido black 10B. Anal. Biochem. 150, 97–104

61. Robb, E. L., Hall, A. R., Prime, T. A., Eaton, S., Szibor, M., Viscomi, C.,

et al. (2018) Control of mitochondrial superoxide production by reverse

electron transfer at complex I. J. Biol. Chem. 293, 9869–9879

62. Rieske, J. S. (1967) Preparation and properties of reduced coenzyme Qcytochrome c reductase (complex III of the respiratory chain). Met.

Enzymol. 10, 239–245

63. Tian, W., Chen, C., Lei, X., and Zhao, J. (2018) CASTp 3.0: computed atlas

of surface topography of proteins. Nucleic Acids Res. 46, W363–W367

Ryo Ikunishi is currently a researcher in the Production Technology Department of Mitsui Chemical Crop & Life Solutions

(Japan) after he completed the Applied Life Science Program at the Graduate School of Agriculture, Kyoto University. His

research focuses on how oversized ubiquinones are catalytically reduced by mitochondrial respiratory complex I, and also

contributes to a better understanding of molecular mechanisms of the inhibitory actions of varying inhibitors in the enzyme.

12 J. Biol. Chem. (2023) 299(8) 105001

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