{"date_published":"2023-03-15T00:00:00Z","publication_status":"published","issue":"5","department":[{"_id":"LeSa"}],"main_file_link":[{"url":"https://doi.org/10.1042/BCJ20210285","open_access":"1"}],"abstract":[{"text":"My group and myself have studied respiratory complex I for almost 30 years, starting in 1994 when it was known as a L-shaped giant ‘black box' of bioenergetics. First breakthrough was the X-ray structure of the peripheral arm, followed by structures of the membrane arm and finally the entire complex from Thermus thermophilus. The developments in cryo-EM technology allowed us to solve the first complete structure of the twice larger, ∼1 MDa mammalian enzyme in 2016. However, the mechanism coupling, over large distances, the transfer of two electrons to pumping of four protons across the membrane remained an enigma. Recently we have solved high-resolution structures of mammalian and bacterial complex I under a range of redox conditions, including catalytic turnover. This allowed us to propose a robust and universal mechanism for complex I and related protein families. Redox reactions initially drive conformational changes around the quinone cavity and a long-distance transfer of substrate protons. These set up a stage for a series of electrostatically driven proton transfers along the membrane arm (‘domino effect'), eventually resulting in proton expulsion from the distal antiporter-like subunit. The mechanism radically differs from previous suggestions, however, it naturally explains all the unusual structural features of complex I. In this review I discuss the state of knowledge on complex I, including the current most controversial issues.","lang":"eng"}],"type":"journal_article","day":"15","article_processing_charge":"No","month":"03","pmid":1,"date_updated":"2023-08-01T13:45:12Z","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"title":"From the 'black box' to 'domino effect' mechanism: What have we learned from the structures of respiratory complex I","quality_controlled":"1","status":"public","oa_version":"Published Version","oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_created":"2023-03-26T22:01:06Z","publisher":"Portland Press","scopus_import":"1","article_type":"review","citation":{"ieee":"L. A. Sazanov, “From the ‘black box’ to ‘domino effect’ mechanism: What have we learned from the structures of respiratory complex I,” <i>The Biochemical Journal</i>, vol. 480, no. 5. Portland Press, pp. 319–333, 2023.","mla":"Sazanov, Leonid A. “From the ‘black Box’ to ‘Domino Effect’ Mechanism: What Have We Learned from the Structures of Respiratory Complex I.” <i>The Biochemical Journal</i>, vol. 480, no. 5, Portland Press, 2023, pp. 319–33, doi:<a href=\"https://doi.org/10.1042/BCJ20210285\">10.1042/BCJ20210285</a>.","short":"L.A. Sazanov, The Biochemical Journal 480 (2023) 319–333.","ama":"Sazanov LA. From the “black box” to “domino effect” mechanism: What have we learned from the structures of respiratory complex I. <i>The Biochemical Journal</i>. 2023;480(5):319-333. doi:<a href=\"https://doi.org/10.1042/BCJ20210285\">10.1042/BCJ20210285</a>","ista":"Sazanov LA. 2023. From the ‘black box’ to ‘domino effect’ mechanism: What have we learned from the structures of respiratory complex I. The Biochemical Journal. 480(5), 319–333.","apa":"Sazanov, L. A. (2023). From the “black box” to “domino effect” mechanism: What have we learned from the structures of respiratory complex I. <i>The Biochemical Journal</i>. Portland Press. <a href=\"https://doi.org/10.1042/BCJ20210285\">https://doi.org/10.1042/BCJ20210285</a>","chicago":"Sazanov, Leonid A. “From the ‘black Box’ to ‘Domino Effect’ Mechanism: What Have We Learned from the Structures of Respiratory Complex I.” <i>The Biochemical Journal</i>. Portland Press, 2023. <a href=\"https://doi.org/10.1042/BCJ20210285\">https://doi.org/10.1042/BCJ20210285</a>."},"_id":"12757","language":[{"iso":"eng"}],"author":[{"first_name":"Leonid A","last_name":"Sazanov","full_name":"Sazanov, Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989"}],"publication":"The Biochemical Journal","has_accepted_license":"1","page":"319-333","doi":"10.1042/BCJ20210285","external_id":{"pmid":["36920092"],"isi":["000957065700001"]},"publication_identifier":{"eissn":["1470-8728"],"issn":["0264-6021"]},"isi":1,"ddc":["570"],"intvolume":"       480","volume":480,"year":"2023"}