{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T21:23:15Z","timestamp":1788643395317,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypoxia\u2013ischemia (HI) is a major cause of brain damage in neonates. Mitochondrial dysfunction acts as a hub for a broad spectrum of signaling events, culminating in cell death triggered by HI. A neuroprotective role of melatonin (MT) has been proposed, and mitophagy regulation seems to be important for cell survival. However, the molecular mechanisms underlying MT\u2010mediated mitophagy during HI treatment are poorly defined. Nucleotide\u2010binding oligomerization domain and leucine\u2010rich repeat\u2010containing protein X1 (NLRX1) has emerged as a critical regulator of mitochondrial dynamics and neuronal death that participates in the pathology of diverse diseases. This study aimed to clarify whether NLRX1 participates in the regulation of mitophagy during MT treatment for hypoxic\u2013ischemic brain damage (HIBD). We demonstrated that MT protected neonates from HIBD through NLRX1\u2010mediated mitophagy in vitro and in vivo. Meanwhile, MT upregulated the expression of NLRX1, Beclin\u20101, and autophagy\u2010related 7 (ATG7) but decreased the expression of the mammalian target of rapamycin (mTOR) and translocase of the inner membrane of mitochondrion 23 (TIM23). Moreover, the neuroprotective effects of MT were abolished by silencing NLRX1 after oxygen\u2013glucose deprivation (OGD). In addition, the downregulation of mTOR and upregulation of Beclin\u20101 and ATG7 by MT were inhibited after silencing NLRX1 under OGD. In summary, MT modulates mitophagy induction through NLRX1 and plays a protective role in HIBD, providing insight into potential therapeutic targets for MT to exert neuroprotection.<\/jats:p>","DOI":"10.1096\/fj.202201523r","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T10:04:53Z","timestamp":1674554693000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Neuroprotective effects of melatonin\u2010mediated mitophagy through nucleotide\u2010binding oligomerization domain and leucine\u2010rich repeat\u2010containing protein\n                    <scp>X1<\/scp>\n                    in neonatal hypoxic\u2013ischemic brain damage"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0975-1495","authenticated-orcid":false,"given":"Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatrics Shengjing Hospital of China Medical University  Shenyang City P.R. 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