--- _id: '1226' abstract: - lang: eng text: Mitochondrial complex I (also known as NADH:ubiquinone oxidoreductase) contributes to cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation across the membrane. It is the largest protein assembly of the respiratory chain with a total mass of 970 kilodaltons. Here we present a nearly complete atomic structure of ovine (Ovis aries) mitochondrial complex I at 3.9 Å resolution, solved by cryo-electron microscopy with cross-linking and mass-spectrometry mapping experiments. All 14 conserved core subunits and 31 mitochondria-specific supernumerary subunits are resolved within the L-shaped molecule. The hydrophilic matrix arm comprises flavin mononucleotide and 8 iron-sulfur clusters involved in electron transfer, and the membrane arm contains 78 transmembrane helices, mostly contributed by antiporter-like subunits involved in proton translocation. Supernumerary subunits form an interlinked, stabilizing shell around the conserved core. Tightly bound lipids (including cardiolipins) further stabilize interactions between the hydrophobic subunits. Subunits with possible regulatory roles contain additional cofactors, NADPH and two phosphopantetheine molecules, which are shown to be involved in inter-subunit interactions. We observe two different conformations of the complex, which may be related to the conformationally driven coupling mechanism and to the active-deactive transition of the enzyme. Our structure provides insight into the mechanism, assembly, maturation and dysfunction of mitochondrial complex I, and allows detailed molecular analysis of disease-causing mutations. article_processing_charge: No article_type: original author: - first_name: Karol full_name: Fiedorczuk, Karol id: 5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0 last_name: Fiedorczuk - first_name: James A full_name: Letts, James A id: 322DA418-F248-11E8-B48F-1D18A9856A87 last_name: Letts orcid: 0000-0002-9864-3586 - first_name: Gianluca full_name: Degliesposti, Gianluca last_name: Degliesposti - first_name: Karol full_name: Kaszuba, Karol id: 3FDF9472-F248-11E8-B48F-1D18A9856A87 last_name: Kaszuba - first_name: Mark full_name: Skehel, Mark last_name: Skehel - first_name: Leonid A full_name: Sazanov, Leonid A id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 citation: ama: Fiedorczuk K, Letts JA, Degliesposti G, Kaszuba K, Skehel M, Sazanov LA. Atomic structure of the entire mammalian mitochondrial complex i. Nature. 2016;538(7625):406-410. doi:10.1038/nature19794 apa: Fiedorczuk, K., Letts, J. A., Degliesposti, G., Kaszuba, K., Skehel, M., & Sazanov, L. A. (2016). Atomic structure of the entire mammalian mitochondrial complex i. Nature. Nature Publishing Group. https://doi.org/10.1038/nature19794 chicago: Fiedorczuk, Karol, James A Letts, Gianluca Degliesposti, Karol Kaszuba, Mark Skehel, and Leonid A Sazanov. “Atomic Structure of the Entire Mammalian Mitochondrial Complex I.” Nature. Nature Publishing Group, 2016. https://doi.org/10.1038/nature19794. ieee: K. Fiedorczuk, J. A. Letts, G. Degliesposti, K. Kaszuba, M. Skehel, and L. A. Sazanov, “Atomic structure of the entire mammalian mitochondrial complex i,” Nature, vol. 538, no. 7625. Nature Publishing Group, pp. 406–410, 2016. ista: Fiedorczuk K, Letts JA, Degliesposti G, Kaszuba K, Skehel M, Sazanov LA. 2016. Atomic structure of the entire mammalian mitochondrial complex i. Nature. 538(7625), 406–410. mla: Fiedorczuk, Karol, et al. “Atomic Structure of the Entire Mammalian Mitochondrial Complex I.” Nature, vol. 538, no. 7625, Nature Publishing Group, 2016, pp. 406–10, doi:10.1038/nature19794. short: K. Fiedorczuk, J.A. Letts, G. Degliesposti, K. Kaszuba, M. Skehel, L.A. Sazanov, Nature 538 (2016) 406–410. date_created: 2018-12-11T11:50:49Z date_published: 2016-10-20T00:00:00Z date_updated: 2021-01-12T06:49:13Z day: '20' department: - _id: LeSa doi: 10.1038/nature19794 ec_funded: 1 external_id: pmid: - '27595392' intvolume: ' 538' issue: '7625' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5164932/ month: '10' oa: 1 oa_version: Submitted Version page: 406 - 410 pmid: 1 project: - _id: 2593EBD6-B435-11E9-9278-68D0E5697425 name: Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (FEBS) - _id: 2590DB08-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '701309' name: Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (H2020) publication: Nature publication_status: published publisher: Nature Publishing Group publist_id: '6108' quality_controlled: '1' scopus_import: 1 status: public title: Atomic structure of the entire mammalian mitochondrial complex i type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 538 year: '2016' ...