{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T22:08:21Z","timestamp":1780351701808,"version":"3.54.1"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2015,9,17]],"date-time":"2015-09-17T00:00:00Z","timestamp":1442448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT094823"],"award-info":[{"award-number":["WT094823"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury.<\/jats:p>","DOI":"10.3390\/ijms160922509","type":"journal-article","created":{"date-parts":[[2015,9,17]],"date-time":"2015-09-17T16:40:26Z","timestamp":1442508026000},"page":"22509-22526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury"],"prefix":"10.3390","volume":"16","author":[{"given":"Ana","family":"Baburamani","sequence":"first","affiliation":[{"name":"Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, St. Thomas' Hospital, SE1 7EH London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Hurling","sequence":"additional","affiliation":[{"name":"Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, St. Thomas' Hospital, SE1 7EH London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Stolp","sequence":"additional","affiliation":[{"name":"Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, St. Thomas' Hospital, SE1 7EH London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Sobotka","sequence":"additional","affiliation":[{"name":"Perinatal Center, Institute for Clinical Sciences and Physiology & Neuroscience,  Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Gressens","sequence":"additional","affiliation":[{"name":"Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, St. Thomas' Hospital, SE1 7EH London, UK"},{"name":"Inserm, U 1141, 75019 Paris, France"},{"name":"University Paris Diderot, Sorbonne Paris Cit\u00e9, UMRS 1141, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Hagberg","sequence":"additional","affiliation":[{"name":"Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, St. Thomas' Hospital, SE1 7EH London, UK"},{"name":"Perinatal Center, Institute for Clinical Sciences and Physiology & Neuroscience,  Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Thornton","sequence":"additional","affiliation":[{"name":"Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, St. Thomas' Hospital, SE1 7EH London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1080\/01443610020025967","article-title":"The relationships between neonatal encephalopathy and cerebral palsy: A cohort study","volume":"21","author":"Evans","year":"2001","journal-title":"J. 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