{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:41:44Z","timestamp":1792626104038,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["19K103"],"award-info":[{"award-number":["19K103"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Necroptosis, a recently described form of programmed cell death, is the main way of alveolar epithelial cells (AECs) death in acute lung injury (ALI). While the mechanism of how to trigger necroptosis in AECs during ALI has been rarely evaluated. Long optic atrophy protein 1 (L\u2010OPA1)\u00a0is a crucial mitochondrial inner membrane fusion protein, and its deficiency impairs mitochondrial function. This study aimed to investigate the role of L\u2010OPA1\u00a0deficiency\u2010mediated mitochondrial dysfunction in AECs necroptosis. We comprehensively investigated the detailed contribution and molecular mechanism of L\u2010OPA1\u00a0deficiency in AECs necroptosis by inhibiting or activating L\u2010OPA1.\u00a0First, our data showed that L\u2010OPA1 expression was downregulated in the lungs and AECs under the lipopolysaccharide (LPS) challenge. Furthermore, inhibition of L\u2010OPA1\u00a0aggravated the pathological injury, inflammatory response, and necroptosis in the lungs of LPS\u2010induced ALI mice. In vitro, inhibition of L\u2010OPA1\u00a0induced necroptosis of AECs, while activation of L\u2010OPA1\u00a0alleviated necroptosis of AECs under the LPS challenge. Mechanistically, inhibition of L\u2010OPA1\u00a0aggravated necroptosis of AECs by inducing mitochondrial fragmentation and reducing mitochondrial membrane potential. While activation of L\u2010OPA1\u00a0had the opposite effects. In summary, these findings indicate for the first time that L\u2010OPA1\u00a0deficiency mediates mitochondrial fragmentation, induces necroptosis of AECs, and exacerbates ALI in mice.<\/jats:p>","DOI":"10.1002\/jcp.30766","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T07:04:11Z","timestamp":1651129451000},"page":"3030-3043","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["L\u2010OPA1 deficiency aggravates necroptosis of alveolar epithelial cells through impairing mitochondrial function during acute lung injury in mice"],"prefix":"10.1002","volume":"237","author":[{"given":"Hui\u2010Ling","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Basic Medicine Science Central South University  Changsha Hunan 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