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If damaged mitochondria cannot be repaired, mitochondrial permeabilization ensues, leading to cell death. Non-optimal turnover of mitochondria is critical as it affects short and long term structural and functional recovery and brain development. Therefore, disposal of deficient mitochondria via mitophagy and their replacement through biogenesis is needed. We utilized mt-Keima reporter mice to quantify mitochondrial morphology (fission, fusion) and mitophagy and their mechanisms in primary neurons after Oxygen Glucose Deprivation (OGD) and in brain sections after neonatal HI. Molecular mechanisms of PARK2-dependent and -independent pathways of mitophagy were investigated in vivo by PCR and Western blotting. Mitochondrial morphology and mitophagy were investigated using live cell microscopy. In primary neurons, we found a primary fission wave immediately after OGD with a significant increase in mitophagy followed by a secondary phase of fission at 24 h following recovery. Following HI, mitophagy was upregulated immediately after HI followed by a second wave at 7 days. Western blotting suggests that both PINK1\/Parkin-dependent and -independent mechanisms, including NIX and FUNDC1, were upregulated immediately after HI, whereas a PINK1\/Parkin mechanism predominated 7 days after HI. We hypothesize that excessive mitophagy in the early phase is a pathologic response which may contribute to secondary energy depletion, whereas secondary mitophagy may be involved in post-HI regeneration and repair.<\/jats:p>","DOI":"10.3390\/cells11071193","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T21:22:39Z","timestamp":1648848159000},"page":"1193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Induction of Mitochondrial Fragmentation and Mitophagy after Neonatal Hypoxia\u2013Ischemia"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8470-2162","authenticated-orcid":false,"given":"Syam","family":"Nair","sequence":"first","affiliation":[{"name":"Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"},{"name":"Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden"},{"name":"Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"Leverin","sequence":"additional","affiliation":[{"name":"Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"},{"name":"Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9342-4691","authenticated-orcid":false,"given":"Eridan","family":"Rocha-Ferreira","sequence":"additional","affiliation":[{"name":"Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"},{"name":"Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden"},{"name":"Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina S.","family":"Sobotka","sequence":"additional","affiliation":[{"name":"Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"},{"name":"Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7676-3272","authenticated-orcid":false,"given":"Claire","family":"Thornton","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Royal Veterinary College, London NW1 0TU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8953-919X","authenticated-orcid":false,"given":"Carina","family":"Mallard","sequence":"additional","affiliation":[{"name":"Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"},{"name":"Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Hagberg","sequence":"additional","affiliation":[{"name":"Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"},{"name":"Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.freeradbiomed.2005.08.040","article-title":"Free radicals, mitochondria, and hypoxia-ischemia in the developing brain","volume":"40","author":"Blomgren","year":"2006","journal-title":"Free Radic. 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