{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:39:10Z","timestamp":1790743150364,"version":"4.1.0"},"reference-count":75,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Brain ischemia\/reperfusion (I\/R) is associated with impairment of mitochondrial function. However, the mechanisms of mitochondrial failure are not fully understood. This work was undertaken to determine the mechanisms and time course of mitochondrial energy dysfunction after reperfusion following neonatal brain hypoxia-ischemia (HI) in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      HI\/reperfusion decreased the activity of mitochondrial complex I, which was recovered after 30\u2009min of reperfusion and then declined again after 1\u2009h. Decreased complex I activity occurred in parallel with a loss in the content of noncovalently bound membrane flavin mononucleotide (FMN). FMN dissociation from the enzyme is caused by succinate-supported reverse electron transfer. Administration of FMN precursor riboflavin before HI\/reperfusion was associated with decreased infarct volume, attenuation of neurological deficit, and preserved complex I activity compared with vehicle-treated mice.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      , the rate of FMN release during oxidation of succinate was not affected by the oxygen level and amount of endogenously produced reactive oxygen species.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>Our data suggest that dissociation of FMN from mitochondrial complex I may represent a novel mechanism of enzyme inhibition defining respiratory chain failure in I\/R. Strategies preventing FMN release during HI and reperfusion may limit the extent of energy failure and cerebral HI injury. The proposed mechanism of acute I\/R-induced complex I impairment is distinct from the generally accepted mechanism of oxidative stress-mediated I\/R injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Our study is the first to highlight a critical role of mitochondrial complex I-FMN dissociation in the development of HI-reperfusion injury of the neonatal brain.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      31, 608\u2013622.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2018.7693","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T07:37:21Z","timestamp":1556609841000},"page":"608-622","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":75,"title":["Redox-Dependent Loss of Flavin by Mitochondrial Complex I in Brain Ischemia\/Reperfusion Injury"],"prefix":"10.1177","volume":"31","author":[{"given":"Anna","family":"Stepanova","sequence":"first","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Columbia University, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Sosunov","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Columbia University, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoya","family":"Niatsetskaya","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Columbia University, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"Konrad","sequence":"additional","affiliation":[{"name":"Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoly A.","family":"Starkov","sequence":"additional","affiliation":[{"name":"Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Manfredi","sequence":"additional","affiliation":[{"name":"Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilka","family":"Wittig","sequence":"additional","affiliation":[{"name":"Functional Proteomics, SFB815 Core Unit, Medical School, Goethe University, Frankfurt, Germany."},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Ten","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Columbia University, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Galkin","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Columbia University, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,7,25]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64052222.x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65041698.x"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0731189.x"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00836.x"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10541-005-0102-7"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi901706w"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199711000-00005"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1159\/000121416"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/185666a0"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3212"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13909"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(89)90148-3"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1511"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25286"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9781139565059"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(73)90442-9"},{"key":"e_1_3_4_18_2","first-page":"644","article-title":"Atomic structure of the entire mammalian mitochondrial complex I","volume":"537","author":"Fiedorczuk K","year":"2016","unstructured":"Fiedorczuk K, , Letts JA, , Degliesposti G, , Kaszuba K, , Skehel M, , and Sazanov LA. 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