{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Agip AA"],"funding":["Medical Research Council","NIH HHS"],"pagination":["e84424"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9977279"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12"],"pubmed_abstract":["Respiratory complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from NADH oxidation by ubiquinone to drive protons across an energy-transducing membrane. <i>Drosophila melanogaster</i> is a candidate model organism for complex I due to its high evolutionary conservation with the mammalian enzyme, well-developed genetic toolkit, and complex physiology for studies in specific cell types and tissues. Here, we isolate complex I from <i>Drosophila</i> and determine its structure, revealing a 43-subunit assembly with high structural homology to its 45-subunit mammalian counterpart, including a hitherto unknown homologue to subunit NDUFA3. The major conformational state of the <i>Drosophila</i> enzyme is the mammalian-type 'ready-to-go' active resting state, with a fully ordered and enclosed ubiquinone-binding site, but a subtly altered global conformation related to changes in subunit ND6. The mammalian-type 'deactive' pronounced resting state is not observed: in two minor states, the ubiquinone-binding site is unchanged, but a deactive-type π-bulge is present in ND6-TMH3. Our detailed structural knowledge of <i>Drosophila</i> complex I provides a foundation for new approaches to disentangle mechanisms of complex I catalysis and regulation in bioenergetics and physiology."],"journal":["eLife"],"pubmed_title":["Cryo-EM structures of mitochondrial respiratory complex I from <i>Drosophila melanogaster</i>."],"pmcid":["PMC9977279"],"funding_grant_id":["MC_UU_00028/1","MC_UU_00028/6","MC_UU_00015/6","MC_UU_00015/2","P40 OD018537"],"pubmed_authors":["Agip AA","Whitworth AJ","Sanchez-Martinez A","Hirst J","Chung I"],"additional_accession":[]},"is_claimable":false,"name":"Cryo-EM structures of mitochondrial respiratory complex I from <i>Drosophila melanogaster</i>.","description":"Respiratory complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from NADH oxidation by ubiquinone to drive protons across an energy-transducing membrane. <i>Drosophila melanogaster</i> is a candidate model organism for complex I due to its high evolutionary conservation with the mammalian enzyme, well-developed genetic toolkit, and complex physiology for studies in specific cell types and tissues. Here, we isolate complex I from <i>Drosophila</i> and determine its structure, revealing a 43-subunit assembly with high structural homology to its 45-subunit mammalian counterpart, including a hitherto unknown homologue to subunit NDUFA3. The major conformational state of the <i>Drosophila</i> enzyme is the mammalian-type 'ready-to-go' active resting state, with a fully ordered and enclosed ubiquinone-binding site, but a subtly altered global conformation related to changes in subunit ND6. The mammalian-type 'deactive' pronounced resting state is not observed: in two minor states, the ubiquinone-binding site is unchanged, but a deactive-type π-bulge is present in ND6-TMH3. Our detailed structural knowledge of <i>Drosophila</i> complex I provides a foundation for new approaches to disentangle mechanisms of complex I catalysis and regulation in bioenergetics and physiology.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2024-12-04T12:39:13.402Z","creation":"2024-12-04T12:39:13.402Z"},"accession":"S-EPMC9977279","cross_references":{"pubmed":["36622099"],"doi":["10.7554/eLife.84424"]}}