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Structures of Respiratory Supercomplex I+III2 Reveal Functional and Conformational Crosstalk.
<div class='caption-title'>Purification of SC I+III2 from Ovine Mitochondria</div>
<div class='caption-title'>NADH:cyt c Oxidoreductase Activity of Isolated SC I+III2</div>
Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA
OpenAccess logo Mol Cell 75 1131-1146.e6 (2019)
Related entries: 6q9b, 6q9d, 6q9e, 6qa9, 6qbx, 6qc2, 6qc3, 6qc4, 6qc5, 6qc6, 6qc7, 6qc8, 6qc9, 6qca

Cited: 81 times
EuropePMC logo PMID: 31492636

Abstract

The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III2 limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII2. CI shows a transition between "closed" and "open" conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII2, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.

Articles - 6qcf mentioned but not cited (1)

  1. Structures of Respiratory Supercomplex I+III2 Reveal Functional and Conformational Crosstalk. Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA. Mol Cell 75 1131-1146.e6 (2019)


Reviews citing this publication (23)

  1. Mitochondrial Metabolism as a Target for Cancer Therapy. Vasan K, Werner M, Chandel NS. Cell Metab 32 341-352 (2020)
  2. The assembly, regulation and function of the mitochondrial respiratory chain. Vercellino I, Sazanov LA. Nat Rev Mol Cell Biol 23 141-161 (2022)
  3. Generation of Reactive Oxygen Species by Mitochondria. Hernansanz-Agustín P, Enríquez JA. Antioxidants (Basel) 10 415 (2021)
  4. Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions. Protasoni M, Zeviani M. Int J Mol Sci 22 E586 (2021)
  5. Architecture of bacterial respiratory chains. Kaila VRI, Wikström M. Nat Rev Microbiol 19 319-330 (2021)
  6. Why All the Fuss about Oxidative Phosphorylation (OXPHOS)? Xu Y, Xue D, Bankhead A, Neamati N. J Med Chem 63 14276-14307 (2020)
  7. Mitochondrial respiratory supercomplexes in mammalian cells: structural versus functional role. Javadov S, Jang S, Chapa-Dubocq XR, Khuchua Z, Camara AK. J Mol Med (Berl) 99 57-73 (2021)
  8. The Mysterious Multitude: Structural Perspective on the Accessory Subunits of Respiratory Complex I. Padavannil A, Ayala-Hernandez MG, Castellanos-Silva EA, Letts JA. Front Mol Biosci 8 798353 (2021)
  9. Regulation and functional role of the electron transport chain supercomplexes. Cogliati S, Cabrera-Alarcón JL, Enriquez JA. Biochem Soc Trans 49 2655-2668 (2021)
  10. Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology. Nesci S, Trombetti F, Pagliarani A, Ventrella V, Algieri C, Tioli G, Lenaz G. Life (Basel) 11 242 (2021)
  11. Structure of respiratory complex I - An emerging blueprint for the mechanism. Kampjut D, Sazanov LA. Curr Opin Struct Biol 74 102350 (2022)
  12. The road to the structure of the mitochondrial respiratory chain supercomplex. Caruana NJ, Stroud DA. Biochem Soc Trans 48 621-629 (2020)
  13. Structure and Mechanism of Respiratory III-IV Supercomplexes in Bioenergetic Membranes. Brzezinski P, Moe A, Ädelroth P. Chem Rev 121 9644-9673 (2021)
  14. Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 Supplementation on Infectious Diseases. Sifuentes-Franco S, Sánchez-Macías DC, Carrillo-Ibarra S, Rivera-Valdés JJ, Zuñiga LY, Sánchez-López VA. Healthcare (Basel) 10 487 (2022)
  15. Making the leap from structure to mechanism: are the open states of mammalian complex I identified by cryoEM resting states or catalytic intermediates? Chung I, Grba DN, Wright JJ, Hirst J. Curr Opin Struct Biol 77 102447 (2022)
  16. Evolution of complex I-like respiratory complexes. Yu H, Schut GJ, Haja DK, Adams MWW, Li H. J Biol Chem 296 100740 (2021)
  17. Age-Related Deterioration of Mitochondrial Function in the Intestine. Schneider AM, Özsoy M, Zimmermann FA, Feichtinger RG, Mayr JA, Kofler B, Sperl W, Weghuber D, Mörwald K. Oxid Med Cell Longev 2020 4898217 (2020)
  18. Research journey of respirasome. Wu M, Gu J, Zong S, Guo R, Liu T, Yang M. Protein Cell 11 318-338 (2020)
  19. Coenzyme Q at the Hinge of Health and Metabolic Diseases. Hernández-Camacho JD, García-Corzo L, Fernández-Ayala DJM, Navas P, López-Lluch G. Antioxidants (Basel) 10 1785 (2021)
  20. Quinone binding sites of cyt bc complexes analysed by X-ray crystallography and cryogenic electron microscopy. Kao WC, Hunte C. Biochem Soc Trans 50 877-893 (2022)
  21. From the 'black box' to 'domino effect' mechanism: what have we learned from the structures of respiratory complex I. Sazanov LA. Biochem J 480 319-333 (2023)
  22. The functional significance of mitochondrial respiratory chain supercomplexes. Kohler A, Barrientos A, Fontanesi F, Ott M. EMBO Rep 24 e57092 (2023)
  23. Organization of the Respiratory Supercomplexes in Cells with Defective Complex III: Structural Features and Metabolic Consequences. Rugolo M, Zanna C, Ghelli AM. Life (Basel) 11 351 (2021)

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  1. Na+ controls hypoxic signalling by the mitochondrial respiratory chain. Hernansanz-Agustín P, Choya-Foces C, Carregal-Romero S, Ramos E, Oliva T, Villa-Piña T, Moreno L, Izquierdo-Álvarez A, Cabrera-García JD, Cortés A, Lechuga-Vieco AV, Jadiya P, Navarro E, Parada E, Palomino-Antolín A, Tello D, Acín-Pérez R, Rodríguez-Aguilera JC, Navas P, Cogolludo Á, López-Montero I, Martínez-Del-Pozo Á, Egea J, López MG, Elrod JW, Ruíz-Cabello J, Bogdanova A, Enríquez JA, Martínez-Ruiz A. Nature 586 287-291 (2020)
  2. Cryo-EM structure of the entire mammalian F-type ATP synthase. Pinke G, Zhou L, Sazanov LA. Nat Struct Mol Biol 27 1077-1085 (2020)
  3. Respiratory supercomplexes act as a platform for complex III-mediated maturation of human mitochondrial complexes I and IV. Protasoni M, Pérez-Pérez R, Lobo-Jarne T, Harbour ME, Ding S, Peñas A, Diaz F, Moraes CT, Fearnley IM, Zeviani M, Ugalde C, Fernández-Vizarra E. EMBO J 39 e102817 (2020)
  4. Mitochondrial complex I structure reveals ordered water molecules for catalysis and proton translocation. Grba DN, Hirst J. Nat Struct Mol Biol 27 892-900 (2020)
  5. Key role of quinone in the mechanism of respiratory complex I. Gutiérrez-Fernández J, Kaszuba K, Minhas GS, Baradaran R, Tambalo M, Gallagher DT, Sazanov LA. Nat Commun 11 4135 (2020)
  6. Functional role of respiratory supercomplexes in mice: SCAF1 relevance and segmentation of the Qpool. Calvo E, Cogliati S, Hernansanz-Agustín P, Loureiro-López M, Guarás A, Casuso RA, García-Marqués F, Acín-Pérez R, Martí-Mateos Y, Silla-Castro JC, Carro-Alvarellos M, Huertas JR, Vázquez J, Enríquez JA. Sci Adv 6 eaba7509 (2020)
  7. High-resolution structure and dynamics of mitochondrial complex I-Insights into the proton pumping mechanism. Parey K, Lasham J, Mills DJ, Djurabekova A, Haapanen O, Yoga EG, Xie H, Kühlbrandt W, Sharma V, Vonck J, Zickermann V. Sci Adv 7 eabj3221 (2021)
  8. A ferredoxin bridge connects the two arms of plant mitochondrial complex I. Klusch N, Senkler J, Yildiz Ö, Kühlbrandt W, Braun HP. Plant Cell 33 2072-2091 (2021)
  9. Multiple pathways coordinate assembly of human mitochondrial complex IV and stabilization of respiratory supercomplexes. Lobo-Jarne T, Pérez-Pérez R, Fontanesi F, Timón-Gómez A, Wittig I, Peñas A, Serrano-Lorenzo P, García-Consuegra I, Arenas J, Martín MA, Barrientos A, Ugalde C. EMBO J 39 e103912 (2020)
  10. Atomic structures of respiratory complex III2, complex IV, and supercomplex III2-IV from vascular plants. Maldonado M, Guo F, Letts JA. Elife 10 e62047 (2021)
  11. Scaf1 promotes respiratory supercomplexes and metabolic efficiency in zebrafish. García-Poyatos C, Cogliati S, Calvo E, Hernansanz-Agustín P, Lagarrigue S, Magni R, Botos M, Langa X, Amati F, Vázquez J, Mercader N, Enríquez JA. EMBO Rep 21 e50287 (2020)
  12. The coupling mechanism of mammalian mitochondrial complex I. Gu J, Liu T, Guo R, Zhang L, Yang M. Nat Struct Mol Biol 29 172-182 (2022)
  13. Atomic structure of a mitochondrial complex I intermediate from vascular plants. Maldonado M, Padavannil A, Zhou L, Guo F, Letts JA. Elife 9 e56664 (2020)
  14. Structures of Tetrahymena's respiratory chain reveal the diversity of eukaryotic core metabolism. Zhou L, Maldonado M, Padavannil A, Guo F, Letts JA. Science 376 831-839 (2022)
  15. Structural insights into NDH-1 mediated cyclic electron transfer. Zhang C, Shuai J, Ran Z, Zhao J, Wu Z, Liao R, Wu J, Ma W, Lei M. Nat Commun 11 888 (2020)
  16. Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV. Vercellino I, Sazanov LA. Nature 598 364-367 (2021)
  17. A universal coupling mechanism of respiratory complex I. Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov L. Nature 609 808-814 (2022)
  18. ND3 Cys39 in complex I is exposed during mitochondrial respiration. Burger N, James AM, Mulvey JF, Hoogewijs K, Ding S, Fearnley IM, Loureiro-López M, Norman AAI, Arndt S, Mottahedin A, Sauchanka O, Hartley RC, Krieg T, Murphy MP. Cell Chem Biol 29 636-649.e14 (2022)
  19. Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. Steiner J, Sazanov L. Elife 9 e59407 (2020)
  20. Cryo-EM grid optimization for membrane proteins. Kampjut D, Steiner J, Sazanov LA. iScience 24 102139 (2021)
  21. Essential role of accessory subunit LYRM6 in the mechanism of mitochondrial complex I. Galemou Yoga E, Parey K, Djurabekova A, Haapanen O, Siegmund K, Zwicker K, Sharma V, Zickermann V, Angerer H. Nat Commun 11 6008 (2020)
  22. Cryo-EM structure of the respiratory I + III2 supercomplex from Arabidopsis thaliana at 2 Å resolution. Klusch N, Dreimann M, Senkler J, Rugen N, Kühlbrandt W, Braun HP. Nat Plants 9 142-156 (2023)
  23. Cryo-electron microscopy reveals how acetogenins inhibit mitochondrial respiratory complex I. Grba DN, Blaza JN, Bridges HR, Agip AA, Yin Z, Murai M, Miyoshi H, Hirst J. J Biol Chem 298 101602 (2022)
  24. Conformational changes in mitochondrial complex I of the thermophilic eukaryote Chaetomium thermophilum. Laube E, Meier-Credo J, Langer JD, Kühlbrandt W. Sci Adv 8 eadc9952 (2022)
  25. Maintenance of complex I and its supercomplexes by NDUF-11 is essential for mitochondrial structure, function and health. Knapp-Wilson A, Pereira GC, Buzzard E, Ford HC, Richardson A, Corey RA, Neal C, Verkade P, Halestrap AP, Gold VAM, Kuwabara PE, Collinson I. J Cell Sci 134 jcs258399 (2021)
  26. Plant-specific features of respiratory supercomplex I + III2 from Vigna radiata. Maldonado M, Fan Z, Abe KM, Letts JA. Nat Plants 9 157-168 (2023)
  27. Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes. Chapa-Dubocq XR, Rodríguez-Graciani KM, Guzmán-Hernández RA, Jang S, Brookes PS, Javadov S. Int J Mol Sci 21 E1555 (2020)
  28. Structure of mycobacterial CIII2CIV2 respiratory supercomplex bound to the tuberculosis drug candidate telacebec (Q203). Yanofsky DJ, Di Trani JM, Król S, Abdelaziz R, Bueler SA, Imming P, Brzezinski P, Rubinstein JL. Elife 10 e71959 (2021)
  29. Cryo-EM structures of engineered active bc1-cbb3 type CIII2CIV super-complexes and electronic communication between the complexes. Steimle S, van Eeuwen T, Ozturk Y, Kim HJ, Braitbard M, Selamoglu N, Garcia BA, Schneidman-Duhovny D, Murakami K, Daldal F. Nat Commun 12 929 (2021)
  30. Cryo-EM structures of mitochondrial respiratory complex I from Drosophila melanogaster. Agip AA, Chung I, Sanchez-Martinez A, Whitworth AJ, Hirst J. Elife 12 e84424 (2023)
  31. Cryo-EM structure of the four-subunit Rhodobacter sphaeroides cytochrome bc1 complex in styrene maleic acid nanodiscs. Swainsbury DJK, Hawkings FR, Martin EC, Musiał S, Salisbury JH, Jackson PJ, Farmer DA, Johnson MP, Siebert CA, Hitchcock A, Hunter CN. Proc Natl Acad Sci U S A 120 e2217922120 (2023)
  32. Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state. Padavannil A, Murari A, Rhooms SK, Owusu-Ansah E, Letts JA. Elife 12 e84415 (2023)
  33. Quinone binding in respiratory complex I: Going through the eye of a needle. The squeeze-in mechanism of passing the narrow entrance of the quinone site. Dhananjayan N, Wang P, Leontyev I, Stuchebrukhov AA. Photochem Photobiol Sci 21 1-12 (2022)
  34. Stable mitochondrial CICIII2 supercomplex interactions in reptiles versus homeothermic vertebrates. Bundgaard A, James AM, Harbour ME, Murphy MP, Fago A. J Exp Biol 223 jeb223776 (2020)
  35. Chlamydomonas reinhardtii as a plant model system to study mitochondrial complex I dysfunction. Subrahmanian N, Castonguay AD, Fatnes TA, Hamel PP. Plant Direct 4 e00200 (2020)
  36. A conserved arginine residue is critical for stabilizing the N2 FeS cluster in mitochondrial complex I. Hameedi MA, Grba DN, Richardson KH, Jones AJY, Song W, Roessler MM, Wright JJ, Hirst J. J Biol Chem 296 100474 (2021)
  37. APOGEE 2: multi-layer machine-learning model for the interpretable prediction of mitochondrial missense variants. Bianco SD, Parca L, Petrizzelli F, Biagini T, Giovannetti A, Liorni N, Napoli A, Carella M, Procaccio V, Lott MT, Zhang S, Vescovi AL, Wallace DC, Caputo V, Mazza T. Nat Commun 14 5058 (2023)
  38. Hypoxia Promotes Mitochondrial Complex I Abundance via HIF-1α in Complex III and Complex IV Eficient Cells. Saldana-Caboverde A, Nissanka N, Garcia S, Lombès A, Diaz F. Cells 9 E2197 (2020)
  39. Leveraging the Entirety of the Protein Data Bank to Enable Improved Structure Prediction Based on Cross-Link Data. Keller A, Chavez JD, Tang X, Bruce JE. J Proteome Res 20 1087-1095 (2021)
  40. Discovery of Mitochondrial Complex I Inhibitors as Anticancer and Radiosensitizer Drugs Based on Compensatory Stimulation of Lactate Release. Lan J, Cadassou O, Corbet C, Riant O, Feron O. Cancers (Basel) 14 5454 (2022)
  41. Investigation of hydrated channels and proton pathways in a high-resolution cryo-EM structure of mammalian complex I. Grba DN, Chung I, Bridges HR, Agip AA, Hirst J. Sci Adv 9 eadi1359 (2023)
  42. Mitochondrial respiratory chain composition and organization in response to changing oxygen levels. Timón-Gómez A, Barrientos A. J Life Sci (Westlake Village) 2 (2020)
  43. Structures of Tetrahymena thermophila respiratory megacomplexes on the tubular mitochondrial cristae. Han F, Hu Y, Wu M, He Z, Tian H, Zhou L. Nat Commun 14 2542 (2023)
  44. Comparative analysis of CI- and CIV-containing respiratory supercomplexes at single-cell resolution. Bertan F, Wischhof L, Scifo E, Guranda M, Jackson J, Marsal-Cots A, Piazzesi A, Stork M, Peitz M, Prehn JHM, Ehninger D, Nicotera P, Bano D. Cell Rep Methods 1 100002 (2021)
  45. Mitochondrial ferredoxin-like is essential for forming complex I-containing supercomplexes in Arabidopsis. Röhricht H, Przybyla-Toscano J, Forner J, Boussardon C, Keech O, Rouhier N, Meyer EH. Plant Physiol 191 2170-2184 (2023)
  46. Single protonation of the reduced quinone in respiratory complex I drives four-proton pumping. Stuchebrukhov AA, Hayashi T. FEBS Lett 597 237-245 (2023)
  47. Structural rather than catalytic role for mitochondrial respiratory chain supercomplexes. Brischigliaro M, Cabrera-Orefice A, Arnold S, Viscomi C, Zeviani M, Fernández-Vizarra E. Elife 12 RP88084 (2023)
  48. Structure of the bc1-cbb3 respiratory supercomplex from Pseudomonas aeruginosa. Di Trani JM, Gheorghita AA, Turner M, Brzezinski P, Ädelroth P, Vahidi S, Howell PL, Rubinstein JL. Proc Natl Acad Sci U S A 120 e2307093120 (2023)
  49. Analysis of Human Clinical Mutations of Mitochondrial ND1 in a Bacterial Model System for Complex I. Alkhaldi HA, Phan DH, Vik SB. Life (Basel) 12 1934 (2022)
  50. Carbon and Nitrogen Sources Have No Impact on the Organization and Composition of Ustilago maydis Respiratory Supercomplexes. Matuz-Mares D, Flores-Herrera O, Guerra-Sánchez G, Romero-Aguilar L, Vázquez-Meza H, Matus-Ortega G, Martínez F, Pardo JP. J Fungi (Basel) 7 42 (2021)
  51. Structural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex. Hryc CF, Mallampalli VKPS, Bovshik EI, Azinas S, Fan G, Serysheva II, Sparagna GC, Baker ML, Mileykovskaya E, Dowhan W. Nat Commun 14 2783 (2023)
  52. Accessory subunit NDUFB4 participates in mitochondrial complex I supercomplex formation. Parmar G, Fong-McMaster C, Pileggi CA, Patten DA, Cuillerier A, Myers S, Wang Y, Hekimi S, Cuperlovic-Culf M, Harper ME. J Biol Chem 300 105626 (2024)
  53. Analysis of the conformational heterogeneity of the Rieske iron-sulfur protein in complex III2 by cryo-EM. Wieferig JP, Kühlbrandt W. IUCrJ 10 27-37 (2023)
  54. Euglena's atypical respiratory chain adapts to the discoidal cristae and flexible metabolism. He Z, Wu M, Tian H, Wang L, Hu Y, Han F, Zhou J, Wang Y, Zhou L. Nat Commun 15 1628 (2024)
  55. Mutation at the entrance of the quinone cavity severely disrupts quinone binding in respiratory complex I. Yi JT, Wang P, Stuchebrukhov AA. Sci Rep 13 20413 (2023)
  56. SCAF1 drives the compositional diversity of mammalian respirasomes. Vercellino I, Sazanov LA. Nat Struct Mol Biol (2024)
  57. Using cryo-EM to understand the assembly pathway of respiratory complex I. Laube E, Schiller J, Zickermann V, Vonck J. Acta Crystallogr D Struct Biol 80 159-173 (2024)


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