{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:43:24Z","timestamp":1791909804339,"version":"4.3.4"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>High levels of inspired oxygen, hyperoxia, are frequently used in patients with acute respiratory failure. Hyperoxia can exacerbate acute respiratory failure, which has high mortality and no specific therapies. We identified novel roles for PTEN-induced putative kinase 1 (PINK1), a mitochondrial protein, and the cytosolic innate immune protein NLRP3 in the lung and endothelium. We generated double knockouts (PINK1\u2212\/\u2212\/NLRP3\u2212\/\u2212), as well as cell-targeted PINK1 silencing and lung-targeted overexpression constructs, to specifically show that PINK1 mediates cytoprotection in wild-type and NLRP3\u2212\/\u2212 mice. The ability to resist hyperoxia is proportional to PINK1 expression. PINK1\u2212\/\u2212 mice were the most susceptible; wild-type mice, which induced PINK1 after hyperoxia, had intermediate susceptibility; and NLRP3\u2212\/\u2212 mice, which had high basal and hyperoxia-induced PINK1, were the least susceptible. Genetic deletion of PINK1 or PINK1 silencing in the lung endothelium increased susceptibility to hyperoxia via alterations in autophagy\/mitophagy, proteasome activation, apoptosis, and oxidant generation.<\/jats:p>","DOI":"10.4049\/jimmunol.1400653","type":"journal-article","created":{"date-parts":[[2014,4,29]],"date-time":"2014-04-29T07:24:55Z","timestamp":1398756295000},"page":"5296-5304","source":"Crossref","is-referenced-by-count":70,"title":["Endothelial PINK1 Mediates the Protective Effects of NLRP3 Deficiency during Lethal Oxidant Injury"],"prefix":"10.1093","volume":"192","author":[{"given":"Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maor","family":"Sauler","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda S","family":"Shinn","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Gong","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Haslip","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiying","family":"Shan","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Mannam","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patty J","family":"Lee","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,6,1]]},"reference":[{"key":"2025032404310768000_r1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1164\/arrd.1980.122.5P2.61","article-title":"Oxygen therapy. Side effects and toxicity","volume":"122","author":"Fisher","year":"1980","journal-title":"Am. Rev. Respir. Dis."},{"key":"2025032404310768000_r2","doi-asserted-by":"crossref","first-page":"C182","DOI":"10.1152\/ajpcell.00086.2013","article-title":"NLRP3 deletion protects from hyperoxia-induced acute lung injury","volume":"305","author":"Fukumoto","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2025032404310768000_r3","doi-asserted-by":"crossref","first-page":"601587","DOI":"10.1155\/2013\/601587","article-title":"Function and characteristics of PINK1 in mitochondria","volume":"2013","author":"Matsuda","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"2025032404310768000_r4","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.immuni.2006.02.004","article-title":"Critical role for NALP3\/CIAS1\/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1","volume":"24","author":"Sutterwala","year":"2006","journal-title":"Immunity"},{"key":"2025032404310768000_r5","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1126\/science.7535475","article-title":"Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme","volume":"267","author":"Kuida","year":"1995","journal-title":"Science"},{"key":"2025032404310768000_r6","doi-asserted-by":"crossref","first-page":"11441","DOI":"10.1073\/pnas.0702717104","article-title":"Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice","volume":"104","author":"Kitada","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404310768000_r7","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.4049\/jimmunol.1300052","article-title":"A protective Hsp70-TLR4 pathway in lethal oxidant lung injury","volume":"191","author":"Zhang","year":"2013","journal-title":"J. Immunol."},{"key":"2025032404310768000_r8","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.4049\/jimmunol.175.8.4834","article-title":"Cutting edge: TLR4 deficiency confers susceptibility to lethal oxidant lung injury","volume":"175","author":"Zhang","year":"2005","journal-title":"J. Immunol."},{"key":"2025032404310768000_r9","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1096\/fj.13-231225","article-title":"Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury","volume":"27","author":"Zhang","year":"2013","journal-title":"FASEB J."},{"key":"2025032404310768000_r10","doi-asserted-by":"crossref","first-page":"10677","DOI":"10.1074\/jbc.M312941200","article-title":"Small interfering RNA targeting heme oxygenase-1 enhances ischemia-reperfusion-induced lung apoptosis","volume":"279","author":"Zhang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2025032404310768000_r11","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1172\/JCI28139","article-title":"Toll-like receptor 4 deficiency causes pulmonary emphysema","volume":"116","author":"Zhang","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025032404310768000_r12","doi-asserted-by":"crossref","first-page":"426","DOI":"10.4161\/auto.19258","article-title":"Autophagic proteins: new facets of the oxygen paradox","volume":"8","author":"Jin","year":"2012","journal-title":"Autophagy"},{"key":"2025032404310768000_r13","doi-asserted-by":"crossref","first-page":"887","DOI":"10.4161\/auto.6767","article-title":"Autophagic proteins regulate cigarette smoke-induced apoptosis: protective role of heme oxygenase-1","volume":"4","author":"Kim","year":"2008","journal-title":"Autophagy"},{"key":"2025032404310768000_r14","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.tcb.2012.05.006","article-title":"Chaperone-mediated autophagy: a unique way to enter the lysosome world","volume":"22","author":"Kaushik","year":"2012","journal-title":"Trends Cell Biol."},{"key":"2025032404310768000_r15","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.cell.2011.02.010","article-title":"PARIS (ZNF746) repression of PGC-1\u03b1 contributes to neurodegeneration in Parkinson\u2019s disease","volume":"144","author":"Shin","year":"2011","journal-title":"Cell"},{"key":"2025032404310768000_r16","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1093\/cvr\/cvs423","article-title":"Nandrolone attenuates aortic adaptation to exercise in rats","volume":"97","author":"Sun","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"2025032404310768000_r17","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1089\/ars.2011.4407","article-title":"Mitophagy: a complex mechanism of mitochondrial removal","volume":"17","author":"Novak","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"2025032404310768000_r18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s13238-011-1127-x","article-title":"The crosstalk between autophagy and apoptosis: where does this lead?","volume":"3","author":"Gordy","year":"2012","journal-title":"Protein Cell"},{"key":"2025032404310768000_r19","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1042\/BJ20111451","article-title":"Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling","volume":"441","author":"Lee","year":"2012","journal-title":"Biochem. J."},{"key":"2025032404310768000_r20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1465-9921-14-97","article-title":"Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells","volume":"14","author":"Hoffmann","year":"2013","journal-title":"Respir. Res."},{"key":"2025032404310768000_r21","doi-asserted-by":"crossref","first-page":"859235","DOI":"10.1155\/2012\/859235","article-title":"Therapeutic potential of heme oxygenase-1\/carbon monoxide in lung disease","volume":"2012","author":"Constantin","year":"2012","journal-title":"Int. J. Hypertens."},{"key":"2025032404310768000_r22","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.4049\/jimmunol.1001654","article-title":"NLRP4 negatively regulates autophagic processes through an association with beclin1","volume":"186","author":"Jounai","year":"2011","journal-title":"J. Immunol."},{"key":"2025032404310768000_r23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.pneurobio.2013.06.002","article-title":"Impaired autophagy and APP processing in Alzheimer\u2019s disease: The potential role of Beclin 1 interactome","volume":"106-107","author":"Salminen","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"2025032404310768000_r24","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10863-009-9253-3","article-title":"The PINK1\/Parkin pathway: a mitochondrial quality control system?","volume":"41","author":"Whitworth","year":"2009","journal-title":"J. Bioenerg. Biomembr."},{"key":"2025032404310768000_r25","doi-asserted-by":"crossref","first-page":"e20655","DOI":"10.1371\/journal.pone.0020655","article-title":"Control of mitochondrial morphology through differential interactions of mitochondrial fusion and fission proteins","volume":"6","author":"Huang","year":"2011","journal-title":"PLoS ONE"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/11\/5296\/62518057\/1400653.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/11\/5296\/62518057\/1400653.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T12:19:06Z","timestamp":1742818746000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/192\/11\/5296\/8001610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,1]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,6,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1400653","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,6]]},"published":{"date-parts":[[2014,6,1]]}}}