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Endothelial cells also regulate tissue perfusion, metabolite exchange, and thrombosis. It is thought that endothelial cells rely on ATP generated via glycolysis, rather than mitochondrial oxidative phosphorylation, to fuel each of these energy-demanding processes. However, endothelial metabolism has mainly been studied in the context of proliferative cells, and little is known about energy production in endothelial cells within the fully formed vascular wall. Using intact arteries isolated from rats and mice, we show that inhibiting mitochondrial respiration disrupts endothelial control of vascular tone. Basal, mechanically activated, and agonist-evoked calcium activity in intact artery endothelial cells are each prevented by inhibiting mitochondrial ATP synthesis. Agonist-evoked calcium activity was also inhibited by blocking the transport of pyruvate, the master fuel for mitochondrial energy production, through the mitochondrial pyruvate carrier. The role for mitochondria in endothelial cell energy production is independent of species, sex, or vascular bed. These data show that a mitochondrial ATP supply is necessary for calcium-dependent, nitric oxide-mediated endothelial control of vascular tone, and identifies the critical role of endothelial mitochondrial energy production in fueling perfused blood vessel function.<\/jats:p>","DOI":"10.1093\/function\/zqac063","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T21:52:26Z","timestamp":1670622746000},"source":"Crossref","is-referenced-by-count":70,"title":["Mitochondrial ATP Production is Required for Endothelial Cell Control of Vascular Tone"],"prefix":"10.1152","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2500-0632","authenticated-orcid":false,"given":"Calum","family":"Wilson","sequence":"first","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , 161 Cathedral Street , Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-382X","authenticated-orcid":false,"given":"Matthew D","family":"Lee","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , 161 Cathedral Street , Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7961-4544","authenticated-orcid":false,"given":"Charlotte","family":"Buckley","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , 161 Cathedral Street , Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , 161 Cathedral Street , Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-3984","authenticated-orcid":false,"given":"John G","family":"McCarron","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , 161 Cathedral Street , Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"issue":"6","key":"2023020909115772000_bib1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.3109\/03014460.2013.807878","article-title":"An estimation of the number of cells in the human body","volume":"40","author":"Bianconi","year":"2013","journal-title":"Ann Hum Biol"},{"issue":"8","key":"2023020909115772000_bib2","doi-asserted-by":"crossref","first-page":"e1002533","DOI":"10.1371\/journal.pbio.1002533","article-title":"Revised estimates for the number of human and bacteria cells in the body","volume":"14","author":"Sender","year":"2016","journal-title":"PLoS Biol"},{"issue":"7","key":"2023020909115772000_bib3","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.cell.2015.05.026","article-title":"Dynamics of cell generation and turnover in the human heart","volume":"161","author":"Bergmann","year":"2015","journal-title":"Cell"},{"issue":"8","key":"2023020909115772000_bib4","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1161\/CIRCRESAHA.111.300233","article-title":"Mitochondria and endothelial function","volume":"112","author":"Kluge","year":"2013","journal-title":"Circ Res"},{"issue":"2","key":"2023020909115772000_bib5","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0167-4889(83)90084-8","article-title":"Metabolic properties of freshly isolated bovine endothelial cells","volume":"762","author":"Dobrina","year":"1983","journal-title":"Biochim Biophys Acta BBA Mol Cell Res"},{"issue":"12","key":"2023020909115772000_bib6","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/0022-2828(90)90984-A","article-title":"Metabolism of exogenous substrates by coronary endothelial cells in culture","volume":"22","author":"Kr\u00fctzfeldt","year":"1990","journal-title":"J Mol Cell Cardiol"},{"issue":"14","key":"2023020909115772000_bib7","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.1073\/pnas.0601026103","article-title":"Mitochondria as signaling organelles in the vascular endothelium","volume":"103","author":"Quintero","year":"2006","journal-title":"Proc Natl Acad Sci"},{"issue":"3","key":"2023020909115772000_bib8","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.cell.2013.06.037","article-title":"Role of PFKFB3-driven glycolysis in vessel sprouting","volume":"154","author":"De\u00a0Bock","year":"2013","journal-title":"Cell"},{"issue":"2","key":"2023020909115772000_bib9","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1083\/jcb.72.2.441","article-title":"Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. 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