{"title":"SCAF1 drives the compositional diversity of mammalian respirasomes","month":"04","_id":"15323","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"ScienComp"}],"doi":"10.1038/s41594-024-01255-0","publication_identifier":{"eissn":["1545-9985"],"issn":["1545-9993"]},"citation":{"chicago":"Vercellino, Irene, and Leonid A Sazanov. “SCAF1 Drives the Compositional Diversity of Mammalian Respirasomes.” <i>Nature Structural and Molecular Biology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41594-024-01255-0\">https://doi.org/10.1038/s41594-024-01255-0</a>.","ieee":"I. Vercellino and L. A. Sazanov, “SCAF1 drives the compositional diversity of mammalian respirasomes,” <i>Nature Structural and Molecular Biology</i>. Springer Nature, 2024.","mla":"Vercellino, Irene, and Leonid A. Sazanov. “SCAF1 Drives the Compositional Diversity of Mammalian Respirasomes.” <i>Nature Structural and Molecular Biology</i>, Springer Nature, 2024, doi:<a href=\"https://doi.org/10.1038/s41594-024-01255-0\">10.1038/s41594-024-01255-0</a>.","ista":"Vercellino I, Sazanov LA. 2024. SCAF1 drives the compositional diversity of mammalian respirasomes. Nature Structural and Molecular Biology.","ama":"Vercellino I, Sazanov LA. SCAF1 drives the compositional diversity of mammalian respirasomes. <i>Nature Structural and Molecular Biology</i>. 2024. doi:<a href=\"https://doi.org/10.1038/s41594-024-01255-0\">10.1038/s41594-024-01255-0</a>","apa":"Vercellino, I., &#38; Sazanov, L. A. (2024). SCAF1 drives the compositional diversity of mammalian respirasomes. <i>Nature Structural and Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-024-01255-0\">https://doi.org/10.1038/s41594-024-01255-0</a>","short":"I. Vercellino, L.A. Sazanov, Nature Structural and Molecular Biology (2024)."},"type":"journal_article","oa_version":"Submitted Version","publisher":"Springer Nature","oa":1,"scopus_import":"1","publication_status":"epub_ahead","author":[{"orcid":"0000-0001-5618-3449","first_name":"Irene","full_name":"Vercellino, Irene","last_name":"Vercellino","id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87"},{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","first_name":"Leonid A","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A"}],"file_date_updated":"2024-05-14T11:57:56Z","language":[{"iso":"eng"}],"department":[{"_id":"LeSa"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2024-04-14T22:01:03Z","publication":"Nature Structural and Molecular Biology","article_processing_charge":"Yes (in subscription journal)","date_published":"2024-04-04T00:00:00Z","year":"2024","file":[{"relation":"main_file","date_updated":"2024-05-14T11:57:56Z","content_type":"application/pdf","file_name":"megacomplex_submit_NSMB_withFigures.pdf","date_created":"2024-05-14T11:57:56Z","file_size":24424729,"checksum":"21f05d188762acd7f49a97f3d09c8d9f","creator":"lsazanov","access_level":"open_access","success":1,"file_id":"15392"}],"ddc":["572"],"external_id":{"pmid":["38575788"]},"has_accepted_license":"1","article_type":"original","project":[{"_id":"627abdeb-2b32-11ec-9570-ec31a97243d3","name":"Structure and mechanism of respiratory chain molecular machines","grant_number":"101020697","call_identifier":"H2020"}],"pmid":1,"acknowledgement":"Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions.","ec_funded":1,"status":"public","abstract":[{"lang":"eng","text":"Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions."}],"tmp":{"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","image":"/images/cc_by.png"},"date_updated":"2024-05-21T08:18:56Z","quality_controlled":"1","day":"04"}