{"doi":"10.1073/pnas.1917968117","title":"Kinetic coupling of the respiratory chain with ATP synthase, but not proton gradients, drives ATP production in cristae membranes","abstract":"<jats:p>\n                    Mitochondria have a characteristic ultrastructure with invaginations of the inner membrane called cristae that contain the protein complexes of the oxidative phosphorylation system. How this particular morphology of the respiratory membrane impacts energy conversion is currently unknown. One proposed role of cristae formation is to facilitate the establishment of local proton gradients to fuel ATP synthesis. Here, we determined the local pH values at defined sublocations within mitochondria of respiring yeast cells by fusing a pH-sensitive GFP to proteins residing in different mitochondrial subcompartments. Only a small proton gradient was detected over the inner membrane in wild type or cristae-lacking cells. Conversely, the obtained pH values did barely permit ATP synthesis in a reconstituted system containing purified yeast F\n                    <jats:sub>1</jats:sub>\n                    F\n                    <jats:sub>0</jats:sub>\n                    ATP synthase, although, thermodynamically, a sufficiently high driving force was applied. At higher driving forces, where robust ATP synthesis was observed, a\n                    <jats:italic>P</jats:italic>\n                    -side pH value of 6 increased the ATP synthesis rate 3-fold compared to pH 7. In contrast, when ATP synthase was coreconstituted with an active proton-translocating cytochrome oxidase, ATP synthesis readily occurred at the measured, physiological pH values. Our study thus reveals that the morphology of the inner membrane does not influence the subcompartmental pH values and is not necessary for robust oxidative phosphorylation in mitochondria. Instead, it is likely that the dense packing of the oxidative phosphorylation complexes in the cristae membranes assists kinetic coupling between proton pumping and ATP synthesis.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":668264,"datarank":0.692268077526189,"base_score":4.61512051684126,"endowment":4.61512051684126,"self_citation_contribution":0.692268077526189,"citation_network_contribution":0.0,"self_endowment_contribution":0.692268077526189,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":100,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1745090,"name":"Axel Meyrat","orcid":null,"position":1,"is_corresponding":false},{"id":1175175,"name":"Stefan Stoldt","orcid":"0009-0000-6798-7629","position":2,"is_corresponding":false},{"id":738904,"name":"Ricardo Santiago","orcid":"0009-0007-9705-9277","position":3,"is_corresponding":false},{"id":1745091,"name":"Dirk Wenzel","orcid":null,"position":4,"is_corresponding":false},{"id":813369,"name":"Stefan Jakobs","orcid":"0000-0002-8028-3121","position":5,"is_corresponding":false},{"id":886218,"name":"Christoph von Ballmoos","orcid":"0000-0002-4642-6088","position":6,"is_corresponding":false},{"id":267911,"name":"Martin Ott","orcid":"0000-0001-6367-3091","position":7,"is_corresponding":false},{"id":1745089,"name":"Alexandra Toth","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Kinetic coupling of the respiratory chain with ATP synthase, but not proton gradients, drives ATP production in cristae membranes","abstract":"<jats:p>\n                    Mitochondria have a characteristic ultrastructure with invaginations of the inner membrane called cristae that contain the protein complexes of the oxidative phosphorylation system. How this particular morphology of the respiratory membrane impacts energy conversion is currently unknown. One proposed role of cristae formation is to facilitate the establishment of local proton gradients to fuel ATP synthesis. Here, we determined the local pH values at defined sublocations within mitochondria of respiring yeast cells by fusing a pH-sensitive GFP to proteins residing in different mitochondrial subcompartments. Only a small proton gradient was detected over the inner membrane in wild type or cristae-lacking cells. Conversely, the obtained pH values did barely permit ATP synthesis in a reconstituted system containing purified yeast F\n                    <jats:sub>1</jats:sub>\n                    F\n                    <jats:sub>0</jats:sub>\n                    ATP synthase, although, thermodynamically, a sufficiently high driving force was applied. At higher driving forces, where robust ATP synthesis was observed, a\n                    <jats:italic>P</jats:italic>\n                    -side pH value of 6 increased the ATP synthesis rate 3-fold compared to pH 7. In contrast, when ATP synthase was coreconstituted with an active proton-translocating cytochrome oxidase, ATP synthesis readily occurred at the measured, physiological pH values. Our study thus reveals that the morphology of the inner membrane does not influence the subcompartmental pH values and is not necessary for robust oxidative phosphorylation in mitochondria. Instead, it is likely that the dense packing of the oxidative phosphorylation complexes in the cristae membranes assists kinetic coupling between proton pumping and ATP synthesis.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.61512051684126,"endowment":4.61512051684126,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31964824","pmcid":"PMC7007565","openalex_id":"https://openalex.org/W3001989577","authors":[],"funders":[{"funder_name":"Knut och Alice Wallenbergs Stiftelse","grant_id":"2013.0006","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"SFB1286","title":null},{"funder_name":"Vetenskapsrådet","grant_id":"2014-4116","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"}],"total_grants":4,"fwci":4.3225,"citation_percentile":0.9574442,"influential_citations":0,"citation_trend":[{"year":2020,"count":4},{"year":2021,"count":18},{"year":2022,"count":10},{"year":2023,"count":26},{"year":2024,"count":15},{"year":2025,"count":17},{"year":2026,"count":10}],"oa_status":"bronze","license":"https://www.pnas.org/site/aboutpnas/licenses.xhtml","oa_locations":[{"url":"https://www.pnas.org/content/pnas/117/5/2412.full.pdf","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/117/5/2412.full.pdf","host_type":"publisher"},{"url":"http://www.pnas.org/syndication/doi/10.1073/pnas.1917968117","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1917968117","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1917968117","host_type":"journal"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7007565","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31964824","host_type":"repository"},{"url":"https://boris-portal.unibe.ch/handle/20.500.12422/37408","host_type":"repository"},{"url":"https://boris.unibe.ch/147126/","host_type":"repository"},{"url":"http://hdl.handle.net/21.11116/0000-0005-93C4-7","host_type":"repository"},{"url":"https://dx.doi.org/10.7892/boris.147126","host_type":""},{"url":"https://dx.doi.org/10.1073/pnas.1917968117","host_type":""},{"url":"https://sonar.ch/global/documents/44441","host_type":""},{"url":"https://sfb1286.uni-goettingen.de/literature/publications/42","host_type":""},{"url":"https://resolver.sub.uni-goettingen.de/purl?gro-2/74534","host_type":""},{"url":"https://hdl.handle.net/21.11116/0000-0005-B816-3","host_type":""},{"url":"https://hdl.handle.net/21.11116/0000-0005-B817-2","host_type":""},{"url":"https://hdl.handle.net/21.11116/0000-0005-93C4-7","host_type":""}],"fields_of_study":["ATP Synthase and ATPases Research","Mitochondrial Function and Pathology","Cancer, Hypoxia, and Metabolism","0301 basic medicine","0303 health sciences","03 medical and health sciences","Adenosine Triphosphate","Electron Transport","Hydrogen-Ion Concentration","Kinetics","Mitochondria","Mitochondrial Membranes","Mitochondrial Proton-Translocating ATPases","Oxidative Phosphorylation","Proteolipids","Proton Pumps","Protons","Saccharomyces cerevisiae"],"mesh_terms":["Adenosine Triphosphate","Electron Transport","Hydrogen-Ion Concentration","Kinetics","Mitochondria","Oxidative Phosphorylation","Proteolipids","Protons","Saccharomyces cerevisiae","Proton Pumps","Mitochondrial Proton-Translocating ATPases","Mitochondrial Membranes"],"keywords":["ATP synthase","Chemiosmosis","Membrane","Coupling (piping)","Proton","F-ATPase","Respiratory chain","Chemistry","Adenosine triphosphate","Biophysics","Mitochondrion","Cell biology","Biochemistry","Biology","Enzyme","Materials science","Physics","Mitochondria","Energy conversion","ATP synthesis","Cristae","Kinetic Coupling","Proteolipids","Saccharomyces cerevisiae","Hydrogen-Ion Concentration","Mitochondrial Proton-Translocating ATPases","Proton Pumps","Oxidative Phosphorylation","Electron Transport","Kinetics","Mitochondrial Membranes","Protons"],"sdg_mappings":[{"sdg_number":7,"sdg_label":"7. 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