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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)


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  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)
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  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)
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  16. Evolution of complex I-like respiratory complexes. Yu H, Schut GJ, Haja DK, Adams MWW, Li H. J Biol Chem 296 100740 (2021)
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  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)
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  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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