{"doi":"10.1093/function/zqab065","title":"ATP Synthase K+- and H+-Fluxes Drive ATP Synthesis and Enable Mitochondrial K+-“Uniporter” Function: I. Characterization of Ion Fluxes","abstract":"Abstract ATP synthase (F1Fo) synthesizes daily our body's weight in ATP, whose production-rate can be transiently increased several-fold to meet changes in energy utilization. Using purified mammalian F1Fo-reconstituted proteoliposomes and isolated mitochondria, we show F1Fo can utilize both ΔΨm-driven H+- and K+-transport to synthesize ATP under physiological pH = 7.2 and K+ = 140 mEq/L conditions. Purely K+-driven ATP synthesis from single F1Fo molecules measured by bioluminescence photon detection could be directly demonstrated along with simultaneous measurements of unitary K+ currents by voltage clamp, both blocked by specific Fo inhibitors. In the presence of K+, compared to osmotically-matched conditions in which this cation is absent, isolated mitochondria display 3.5-fold higher rates of ATP synthesis, at the expense of 2.6-fold higher rates of oxygen consumption, these fluxes being driven by a 2.7:1 K+: H+ stoichiometry. The excellent agreement between the functional data obtained from purified F1Fo single molecule experiments and ATP synthase studied in the intact mitochondrion under unaltered OxPhos coupling by K+ presence, is entirely consistent with K+ transport through the ATP synthase driving the observed increase in ATP synthesis. Thus, both K+ (harnessing ΔΨm) and H+ (harnessing its chemical potential energy, ΔμH) drive ATP generation during normal physiology.","journal":"Function","year":2021,"id":163204,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":682049,"name":"Evgeny Kobrinsky","orcid":"0000-0001-6883-9900","position":1,"is_corresponding":false},{"id":471092,"name":"Dmitry B. Zorov","orcid":"0000-0003-0863-8490","position":2,"is_corresponding":false},{"id":682782,"name":"Hanne Nuss","orcid":null,"position":3,"is_corresponding":false},{"id":559078,"name":"Yael Yaniv","orcid":"0000-0002-5183-6284","position":4,"is_corresponding":false},{"id":291051,"name":"Kenneth W. Fishbein","orcid":"0000-0002-6353-4603","position":5,"is_corresponding":false},{"id":258549,"name":"Rafael de Cabo","orcid":"0000-0003-2830-5693","position":6,"is_corresponding":false},{"id":435565,"name":"Lluı́s Montoliu","orcid":"0000-0003-3941-1176","position":7,"is_corresponding":false},{"id":434249,"name":"Sandra B. Gabelli","orcid":"0000-0003-1205-5204","position":8,"is_corresponding":false},{"id":258544,"name":"Miguel A. Aon","orcid":"0000-0002-4355-5431","position":9,"is_corresponding":false},{"id":383578,"name":"Sonia Cortassa","orcid":"0000-0001-7224-9858","position":10,"is_corresponding":false},{"id":471093,"name":"Steven J. Sollott","orcid":"0000-0003-1730-2956","position":11,"is_corresponding":false},{"id":286635,"name":"Magdalena Juhaszova","orcid":"0000-0001-9571-9541","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-18T23:45:17.971865Z","pmid":"35229078","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}