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Structural Studies of Respirasome by Cryo-Electron Microscopy
Applied Microscopy 2018;48:81-6
Published online December 28, 2018
© 2018 Korean Society of Microscopy.

Tae Jin Jeon, Ho Min Kim1, and Seong Eon Ryu*

Department of Bioengineering, College of Engineering, Hanyang University, Seoul 04763, Korea, 1Graduate School of Medical Science & Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea
Correspondence to: Ryu SE, http://orcid.org/0000-0003-3335-326X, Tel: +82-2-2220-4020, Fax: +82-2-2220-4023, E-mail: ryuse@hanyang.ac.kr
Received October 25, 2018; Revised November 21, 2018; Accepted November 22, 2018.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract

The respiratory chain complex forms a supercomplex (SC) in the inner mitochondrial membrane. This complex facilitates the process of electron transfer to produce the proton gradient used to synthesize ATP. Understanding the precise structure of the SC is considered an important challenge. However, it has not yet been reported. The development of a Cryo-electron microscopy (EM) technique provides an effective way to obtain high-resolution micrographs to determine the high-resolution three-dimensional structure of biomolecules. In this brief review, the currently reported Cryo-EM structures of the mammalian respirasome have been described in order to establish a direction for further research in the respiratory system.

Keywords : Cryo-electron microscopy, Biomolecule structure, Respiratory chain complex, Respirasome
References
  1. Agip, AA, Blaza, JN, Bridges, HR, Viscomi, C, Rawson, S, Muench, SP, and Hirst, J (2018). Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states. Nat Struct Mol Biol. 25, 548-556.
    Pubmed KoreaMed CrossRef
  2. Ai, Q, Jing, Y, Jiang, R, Lin, L, Dai, J, Che, Q, Zhou, D, Jia, M, Wan, J, and Zhang, L (2014). Rotenone, a mitochondrial respiratory complex I inhibitor, ameliorates lipopolysaccharide/D-galactosamine-induced fulminant hepatitis in mice. Int Immunopharmacol. 21, 200-207.
    Pubmed CrossRef
  3. Alam, M, and Schmidt, WJ (2004). Mitochondrial complex I inhibition depletes plasma testosterone in the rotenone model of Parkinson’s disease. Physiol Behav. 83, 395-400.
    Pubmed CrossRef
  4. Althoff, T, Mills, DJ, Popot, JL, and Kuhlbrandt, W (2011). Arrangement of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1. EMBO J. 30, 4652-4664.
    Pubmed KoreaMed CrossRef
  5. Angerer, H, Zwicker, K, Wumaier, Z, Sokolova, L, Heide, H, Steger, M, Kaiser, S, Nubel, E, Brutschy, B, Radermacher, M, Brandt, T, and Zickermann, V (2011). A scaffold of accessory subunits links the peripheral arm and the distal proton-pumping module of mitochondrial complex I. Biochem J. 437, 279-288.
    Pubmed KoreaMed CrossRef
  6. Baradaran, R, Berrisford, JM, Minhas, GS, and Sazanov, LA (2013). Crystal structure of the entire respiratory complex I. Nature. 494, 443-448.
    Pubmed KoreaMed CrossRef
  7. Bianchi, C, Fato, R, Genova, ML, Castelli, GP, and Lenaz, G (2003). Structural and functional organization of Complex I in the mitochondrial respiratory chain. BioFactors. 18, 3-9.
    Pubmed CrossRef
  8. Bianchi, C, Genova, ML, Castelli, GP, and Lenaz, G (2004). The mitochondrial respiratory chain is partially organized in a supercomplex assembly - Kinetic evidence using flux control analysis. J Biol Chem. 279, 36562-36569.
    Pubmed CrossRef
  9. Blaza, JN, Serreli, R, Jones, AJ, Mohammed, K, and Hirst, J (2014). Kinetic evidence against partitioning of the ubiquinone pool and the catalytic relevance of respiratory-chain supercomplexes. Proc Natl Acad Sci USA. 111, 15735-15740.
    Pubmed KoreaMed CrossRef
  10. Blaza, JN, Vinothkumar, KR, and Hirst, J (2018). Structure of the deactive state of mammalian respiratory complex I. Structure. 26, 312-319.
    Pubmed KoreaMed CrossRef
  11. Bonora, M, Patergnani, S, Rimessi, A, De, ME, Suski, JM, Bononi, A, Giorgi, C, Marchi, S, Missiroli, S, Poletti, F, Wieckowski, MR, and Pinton, P (2012). ATP synthesis and storage. Purinergic Signal. 8, 343-357.
    Pubmed KoreaMed CrossRef
  12. Carroll, J, Fearnley, IM, Shannon, RJ, Hirst, J, and Walker, JE (2003). Analysis of the subunit composition of complex I from bovine heart mitochondria. Mol Cell Proteomics. 2, 117-126.
    Pubmed CrossRef
  13. Carroll, J, Fearnley, IM, Skehel, JM, Shannon, RJ, Hirst, J, and Walker, JE (2006). Bovine complex I is a complex of 45 different subunits. J Biol Chem. 281, 32724-32727.
    Pubmed CrossRef
  14. Chouchani, ET, Methner, C, Nadtochiy, SM, Logan, A, Pell, VR, Ding, S, James, AM, Cocheme, HM, Reinhold, J, Lilley, KS, Partridge, L, Fearnley, IM, Robinson, AJ, Hartley, RC, Smith, RA, Krieg, T, Brookes, PS, and Murphy, MP (2013). Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat Med. 19, 753-759.
    Pubmed KoreaMed CrossRef
  15. Chung, JH, and Kim, HM (2017). The nobel prize in chemistry 2017: high-resolution cryo-electron microscopy. Appl Microsc. 47, 218-222.
    CrossRef
  16. Chung, JM, and Jung, HS (2018). Cryo-electron tomography: a tool for in situ structural analysis of macromolecular complexes. Appl Spectrosc Rev. 53, 195-202.
    CrossRef
  17. Darrouzet, E, Issartel, JP, Lunardi, J, and Dupuis, A (1998). The 49-kDa subunit of NADH-ubiquinone oxidoreductase (Complex I) is involved in the binding of piericidin and rotenone, two quinone-related inhibitors. FEBS Lett. 431, 34-38.
    Pubmed CrossRef
  18. Dudkina, NV, Kudryashev, M, Stahlberg, H, and Boekema, EJ (2011). Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography. Proc Natl Acad Sci USA. 108, 15196-15200.
    Pubmed KoreaMed CrossRef
  19. Dudkina, NV, Sunderhaus, S, Boekema, EJ, and Braun, HP (2008). The higher level of organization of the oxidative phosphorylation system: mitochondrial supercomplexes. J Bioenerg Biomembr. 40, 419-424.
    Pubmed KoreaMed CrossRef
  20. Efremov, RG, Baradaran, R, and Sazanov, LA (2010). The architecture of respiratory complex I. Nature. 465, 441-445.
    Pubmed CrossRef
  21. Enriquez, JA (2016). Supramolecular organization of respiratory complexes. Annu Rev Physiol. 78, 533-561.
    Pubmed CrossRef
  22. Fiedorczuk, K, Letts, JA, Degliesposti, G, Kaszuba, K, Skehel, M, and Sazanov, LA (2016). Atomic structure of the entire mammalian mitochondrial complex I. Nature. 538, 406-410.
    Pubmed KoreaMed CrossRef
  23. Fowler, LR, and Richardson, SH (1963). Studies on the electron transfer system. J Biol Chem. 238, 456-463.
    Pubmed
  24. Gao, X, Wen, X, Esser, L, Quinn, B, Yu, L, Yu, CA, and Xia, D (2003). Structural basis for the quinone reduction in the bc1 complex: a comparative analysis of crystal structures of mitochondrial cytochrome bc1 with bound substrate and inhibitors at the Qi site. Biochemistry. 42, 9067-9080.
    Pubmed CrossRef
  25. Grgic, L, Zwicker, K, Kashani-Poor, N, Kerscher, S, and Brandt, U (2004). Functional significance of conserved histidines and arginines in the 49-kDa subunit of mitochondrial complex I. J Biol Chem. 279, 21193-21199.
    Pubmed CrossRef
  26. Gu, J, Wu, M, Guo, R, Yan, K, Lei, J, Gao, N, and Yang, M (2016). The architecture of the mammalian respirasome. Nature. 537, 639-643.
    Pubmed CrossRef
  27. Guo, R, Zong, S, Wu, M, Gu, J, and Yang, M (2017). Architecture of human mitochondrial respiratory megacomplex I2III2IV2. Cell. 170, 1247-1257.
    CrossRef
  28. Hatefi, Y (1985). The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem. 54, 1015-1069.
    Pubmed CrossRef
  29. Hirst, J, Carroll, J, Fearnley, IM, Shannon, RJ, and Walker, JE (2003). The nuclear encoded subunits of complex I from bovine heart mitochondria. Biochim Biophys Acta. 1604, 135-150.
    Pubmed CrossRef
  30. Iwata, S, Lee, JW, Okada, K, Lee, JK, Iwata, M, Rasmussen, B, Link, TA, Ramaswamy, S, and Jap, BK (1998). Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. Science. 281, 64-71.
    Pubmed CrossRef
  31. Jonckheere, AI, Smeitink, JAM, and Rodenburg, RJT (2012). Mitochondrial ATP synthase: architecture, function and pathology. J Inherit Metab Dis. 35, 211-225.
    KoreaMed CrossRef
  32. Kashani-Poor, N, Zwicker, K, Kerscher, S, and Brandt, U (2001). A central functional role for the 49-kDa subunit within the catalytic core of mitochondrial complex I. J Biol Chem. 276, 24082-24087.
    Pubmed CrossRef
  33. Letts, JA, Fiedorczuk, K, and Sazanov, LA (2016). The architecture of respiratory supercomplexes. Nature. 537, 644-648.
    Pubmed CrossRef
  34. Letts, JA, and Sazanov, LA (2017). Clarifying the supercomplex: the higher-order organization of the mitochondrial electron transport chain. Nat Struct Mol Biol. 24, 800-808.
    Pubmed CrossRef
  35. Lopez-Fabuel, I, Le Douce, J, Logan, A, James, AM, Bonvento, G, Murphy, MP, Almeida, A, and Bolanos, JP (2016). Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes. Proc Natl Acad Sci USA. 113, 13063-13068.
    Pubmed KoreaMed CrossRef
  36. Maranzana, E, Barbero, G, Falasca, AI, Lenaz, G, and Genova, ML (2013). Mitochondrial respiratory supercomplex association limits production of reactive oxygen species from complex I. Antioxid Redox Signal. 19, 1469-1480.
    Pubmed KoreaMed CrossRef
  37. Mitchell, P (1975a). The protonmotive Q cycle: a general formulation. FEBS Lett. 59, 137-139.
    CrossRef
  38. Mitchell, P (1975b). Protonmotive redox mechanism of the cytochrome b-c1 complex in the respiratory chain: protonmotive ubiquinone cycle. FEBS Lett. 56, 1-6.
    CrossRef
  39. Parey, K, Brandt, U, Xie, H, Mills, DJ, Siegmund, K, Vonck, J, Kuhlbrandt, W, and Zickermann, V (2018). Cryo-EM structure of respiratory complex I at work. eLife. 7, e39213.
    Pubmed KoreaMed CrossRef
  40. Pettersen, EF, Goddard, TD, Huang, CC, Couch, GS, Greenblatt, DM, Meng, EC, and Ferrin, TE (2004). UCSFChimera--a visualization system for exploratory research and analysis. J Comput Chem. 25, 1605-1612.
    Pubmed CrossRef
  41. Pietras, R, Sarewicz, M, and Osyczka, A (2016). Distinct properties of semi-quinone species detected at the ubiquinol oxidation Q(o) site of cytochrome bc(1) and their mechanistic implications. J R Soc Interface. 13, 20160133.
    CrossRef
  42. Sarewicz, M, and Osyczka, A (2015). Electronic connection between the quinone and cytochrome c redox pools and its role in regulation of mitochondrial electron transport and redox signaling. Physiol Rev. 95, 219-243.
    KoreaMed CrossRef
  43. Sazanov, LA (2015). A giant molecular proton pump: structure and mechanism of respiratory complex I. Nat Rev Mol Cell Biol. 16, 375-388.
    Pubmed CrossRef
  44. Sousa, JS, Mills, DJ, Vonck, J, and Kuhlbrandt, W (2016). Functional asymmetry and electron flow in the bovine respirasome. eLife. 5, e21290.
    Pubmed KoreaMed CrossRef
  45. Tocilescu, MA, Fendel, U, Zwicker, K, Kerscher, S, and Brandt, U (2007). Exploring the ubiquinone binding cavity of respiratory complex I. J Biol Chem. 282, 29514-29520.
    Pubmed CrossRef
  46. Tocilescu, MA, Zickermann, V, Zwicker, K, and Brandt, U (2010). Quinone binding and reduction by respiratory complex I. Biochim Biophys Acta. 1797, 1883-1890.
    Pubmed CrossRef
  47. Vinothkumar, KR, Zhu, J, and Hirst, J (2014). Architecture of mammalian respiratory complex I. Nature. 515, 80-84.
    Pubmed KoreaMed CrossRef
  48. Walker, JE (1992). The NADH:ubiquinone oxidoreductase (complex I) of respiratory chains. Q Rev Biophys. 25, 253-324.
    Pubmed CrossRef
  49. Wallace, DC (2012). Mitochondria and cancer. Nat Rev Cancer. 12, 685-698.
    Pubmed KoreaMed CrossRef
  50. Watabe, M, and Nakaki, T (2008). Mitochondrial complex I inhibitor rotenone inhibits and redistributes vesicular monoamine transporter 2 via nitration in human dopaminergic SH-SY5Y cells. Mol Pharmacol. 74, 933-940.
    Pubmed CrossRef
  51. Wirth, C, Brandt, U, Hunte, C, and Zickermann, V (2016). Structure and function of mitochondrial complex I. Biochim Biophys Acta. 1857, 902-914.
    Pubmed CrossRef
  52. Wu, M, Gu, J, Guo, R, Huang, Y, and Yang, M (2016). Structure of mammalian respiratory supercomplex I1III2IV1. Cell. 167, 1598-1609.
    CrossRef
  53. Zhu, J, Vinothkumar, KR, and Hirst, J (2016). Structure of mammalian respiratory complex I. Nature. 536, 354-358.
    Pubmed KoreaMed CrossRef
  54. Zickermann, V, Wirth, C, Nasiri, H, Siegmund, K, Schwalbe, H, Hunte, C, and Brandt, U (2015). Mechanistic insight from the crystal structure of mitochondrial complex I. Science. 347, 44-49.
    Pubmed CrossRef

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