{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:51:47Z","timestamp":1791305507461,"version":"4.3.1"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIAID","award":["5PO1AI106684-09"],"award-info":[{"award-number":["5PO1AI106684-09"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH","award":["5R01AI145406-05"],"award-info":[{"award-number":["5R01AI145406-05"]}]},{"name":"NIH","award":["HL153058"],"award-info":[{"award-number":["HL153058"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Type 2 (T2) inflammation is a defining feature of asthma and associated with epithelial dysfunction, including goblet cell metaplasia and ciliary loss. Here, we investigated whether T2 inflammation and associated 15 lipoxygenase-1 (15LO1) activity alters mitochondrial metabolism in airway epithelial cells (AECs) and contributes to disease pathophysiology. Freshly isolated AECs from T2-high asthmatic participants exhibited increased oxygen consumption rates (OCR), including elevated basal respiration and proton leak, alongside reduced coupling efficiency compared to T2-low participants. These functional changes were accompanied by increased expression of electron transport chain (ETC) proteins, worse lung function and epithelial phenotypic changes.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , IL-13 stimulation of differentiated AECs recapitulated these findings, inducing higher OCR, increased ETC protein levels, and enhanced proton leak while paradoxically reducing intracellular ATP. These metabolic alterations are associated with increased uncoupling protein 2 (UCP2) expression and goblet cell differentiation. Mechanistically, 15LO1 emerged as a key regulator, as ALOX15 knockdown or pharmacologic inhibition reduced OCR parameters, ETC protein expression, UCP2, and goblet cell markers, without effect on ATP levels, suggesting additional regulatory mechanisms. Collectively, these findings identify a metabolic axis linking T2 inflammation, mitochondrial dysfunction, and airway epithelial metabolism, while highlighting 15LO1-driven mitochondrial uncoupling as a potential therapeutic target in asthma.\u2003\n                  <\/jats:p>","DOI":"10.1172\/jci200067","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:00:41Z","timestamp":1791302441000},"source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial metabolic dysfunction in airway epithelial cells promotes goblet cell metaplasia and more severe asthma"],"prefix":"10.1172","author":[{"given":"Xiuxia","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krithika S.","family":"Rao","sequence":"additional","affiliation":[{"name":"Vascular Medicine Institute, Division of Cardiology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sruti","family":"Shiva","sequence":"additional","affiliation":[{"name":"Vascular Medicine Institute, Division of Classical Hematology, Department o, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"van Heusden","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayoko","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Kendi","sequence":"additional","affiliation":[{"name":"Vascular Medicine Institute, Division of Cardiology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura R.","family":"Bradley","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0473-2730","authenticated-orcid":true,"given":"John B.","family":"Trudeau","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Ray","sequence":"additional","affiliation":[{"name":"Pulmonary, Allergy, Critical Care, and Sleep Medicine Division, Department , School of Medicine, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Boucher","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7761-9109","authenticated-orcid":true,"given":"Sally E.","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,6]]},"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.jci.org\/articles\/view\/200067\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:00:43Z","timestamp":1791302443000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jci.org\/articles\/view\/200067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":0,"alternative-id":["10.1172\/JCI200067"],"URL":"https:\/\/doi.org\/10.1172\/jci200067","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]}}}