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Our previous work demonstrates that oxidant and mitochondrial injury play a critical role in hyperoxia-induced acute lung injury (HALI). Recently, thyroid hormone has been demonstrated to promote mitochondrial survival in other models of lung injury, but its role in hyperoxia is unknown. Adult wild-type (WT) mice were pretreated with either nebulized triiodothyronine (T3, 40\u2009\u03bcg\/kg) for 1 or 3\u2009days, or with propylthiouracil (PTU, 100\u2009\u03bcg\/kg), for 3\u2009days. Following pretreatment, WT mice underwent 72\u2009h of hyperoxia exposure. WT and PINK1<jats:sup>\u2212\/\u2212<\/jats:sup> mice were pretreated with either nebulized T3 (40\u2009\u03bcg\/kg) for 3\u2009days or no pretreatment before 72\u2009h continuous hyperoxia exposure. Bronchoalveolar lavage (BAL), histological changes in cellular composition, and type I cytokine induction were assessed. Lung lysates for mitochondrial cellular bioenergetics markers were analyzed by Western blot. Hyperoxia caused a significant increase in BAL total cell counts and lung cellular infiltrates. Administration of PTU enhanced HALI, whereas T3 attenuated HALI, inflammation, and oxidants in WT mice. In addition, T3 pretreatment increased mitochondrial biogenesis\/fusion\/mitophagy and decreased ER stress and apoptosis. PINK1<jats:sup>\u2212\/\u2212<\/jats:sup> mice were more susceptible to hyperoxia than WT mice. Notably, pretreatment with T3 did not attenuate HALI in PINK1<jats:sup>\u2212\/\u2212<\/jats:sup> mice. In addition, T3 pretreatment increased mitochondrial anti-ROS potential, improved mitochondrial bioenergetics and mitophagy, and attenuated mitochondria-regulated apoptosis, all in a PINK1-dependent manner. Our results highlight a novel protective role for PINK1 in mediating the cytoprotective effects of thyroid hormone in HALI. Therefore, thyroid hormone may represent a potential therapy for ALI. <\/jats:p>","DOI":"10.1152\/ajplung.00598.2020","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T12:02:14Z","timestamp":1618401734000},"page":"L1118-L1125","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["PINK1 mediates the protective effects of thyroid hormone T3 in hyperoxia-induced lung injury"],"prefix":"10.1152","volume":"320","author":[{"given":"Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Henan Normal University Xinxiang, Xinxiang, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5917-4601","authenticated-orcid":true,"given":"Naftali","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patty J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut"},{"name":"Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Duke University School of Medicine, Durham, North Carolina"},{"name":"Pulmonary & Critical Care, Durham VA Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2016.08.010"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101679"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1061849"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1511263"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400653"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0007"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/bs.vh.2017.06.001"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00376.2002"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0179OC"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms141223893"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4447"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109926108"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200709-1429OC"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-15-0133"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00225-9"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2020.03.060"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304865"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2018.7514"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/crj.12418"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199112000-00005"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajplung.00598.2020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T08:43:13Z","timestamp":1624437793000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajplung.00598.2020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,1]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6,1]]}},"alternative-id":["10.1152\/ajplung.00598.2020"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00598.2020","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,1]]},"assertion":[{"value":"2020-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}