{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:46:04Z","timestamp":1793364364441,"version":"4.5.0"},"reference-count":35,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Innovative Talent Program of Zhejiang Health Department","award":["2020RC012"],"award-info":[{"award-number":["2020RC012"]}]},{"name":"Key Program of Zhejiang","award":["WKJ-ZJ-2004"],"award-info":[{"award-number":["WKJ-ZJ-2004"]}]},{"name":"Key R&D Program of Zhejiang","award":["2022C03133"],"award-info":[{"award-number":["2022C03133"]}]},{"name":"Zheng Shu Medical Elite Scholarship Fund","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971099, 82171273, 82171275 and 82202407"],"award-info":[{"award-number":["81971099, 82171273, 82171275 and 82202407"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ20H090015"],"award-info":[{"award-number":["LQ20H090015"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Stroke Vasc Neurol"],"accepted":{"date-parts":[[2023,9,15]]},"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ischaemic stroke triggers neuronal mitophagy, while the involvement of mitophagy receptors in ischaemia\/reperfusion (I\/R) injury-induced neuronal mitophagy remain not fully elucidated. Here, we aimed to investigate the involvement of mitophagy receptor FUN14 domain-containing 1 (FUNDC1) and its modulation in neuronal mitophagy induced by I\/R injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Wild-type and FUNDC1 knockout mice were generated to establish models of neuronal I\/R injury, including transient middle cerebral artery occlusion (tMCAO) in vivo and oxygen glucose deprivation\/reperfusion in vitro. Stroke outcomes of mice with two genotypes were assessed. Neuronal mitophagy was analysed both in vivo and in vitro. Activities of FUNDC1 and its regulator Src were evaluated. The impact of Src on FUNDC1-mediated mitophagy was assessed through administration of Src antagonist PP1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>To our surprise, FUNDC1 knockout mice subjected to tMCAO showed stroke outcomes comparable to those of their wild-type littermates. Although neuronal mitophagy could be activated by I\/R injury, FUNDC1 deletion did not disrupt neuronal mitophagy. Transient activation of FUNDC1, represented by dephosphorylation of Tyr18, was detected in the early stages (within 3\u2009hours) of neuronal I\/R injury; however, phosphorylated Tyr18 reappeared and even surpassed baseline levels in later stages (after 6\u2009hours), accompanied by a decrease in FUNDC1-light chain 3 interactions. Spontaneous inactivation of FUNDC1 was associated with Src activation, represented by phosphorylation of Tyr416, which changed in parallel with the level of phosphorylated FUNDC1 (Tyr18) during neuronal I\/R injury. Finally, FUNDC1-mediated mitophagy in neurons under I\/R conditions can be rescued by pharmacological inhibition of Src.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FUNDC1 is inactivated by Src during the later stage (after 6\u2009hours) of neuronal I\/R injury, and rescue of FUNDC1-mediated mitophagy may serve as a potential therapeutic strategy for treating ischaemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/svn-2023-002606","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T14:30:30Z","timestamp":1696429830000},"page":"367-379","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":44,"title":["Src inhibition rescues FUNDC1-mediated neuronal mitophagy in ischaemic stroke"],"prefix":"10.1136","volume":"9","author":[{"given":"Tianchi","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-bin","family":"Hu","sequence":"additional","affiliation":[{"name":"Neurosurgery, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Ding","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfeng","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong-jie","family":"Fu","sequence":"additional","affiliation":[{"name":"Neurosurgery, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangnan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang University Department of Pharmacology, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao","family":"Chen","sequence":"additional","affiliation":[{"name":"Neurosurgery, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8412-7865","authenticated-orcid":false,"given":"Jianru","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,10,4]]},"reference":[{"key":"2025081709333576000_9.4.367.1","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.tips.2016.06.007","article-title":"Targeting oxidative stress in central nervous system disorders","volume":"37","author":"Patel","year":"2016","journal-title":"Trends Pharmacol 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