{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T21:10:09Z","timestamp":1758748209498,"version":"3.44.0"},"reference-count":77,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006978","name":"University of California Berkeley","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100006978","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100030613","name":"Ford Foundation Fellowships","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100030613","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"Abstract<\/jats:title>Sea turtles experience extreme fluctuations in oxygen levels derived from extended breath\u2010hold diving, yet the cellular adjustments underlying hypoxia tolerance in these animals remain poorly understood. Here, we employed metabolite profiling, extracellular flux assays and microscopy analyses of the mitochondrial reticulum to investigate how primary cells derived from sea turtles and lizards cope with extended hypoxia exposure. Cells from both species proliferate in primary culture, stain positive for fibroblast markers, are metabolically active and stabilize HIF1\u2010\u03b1 when exposed to chemical or environmental hypoxia. In contrast to lizard cells, sea turtle cells exhibit a faster and more robust response to 1\u00a0h or 24\u00a0h of hypoxia exposure (0.1% O2<\/jats:sub>), upregulating antioxidant pathways and optimizing oxygen use rather than relying on glycolytic metabolism. Similarly, mitochondrial reticulum architecture is maintained without apparent fragmentation during hypoxia exposure in sea turtle cells. Consistent with these observations, sea turtle mitochondria maintain better function during reoxygenation following 24\u00a0h of hypoxia exposure. These findings show that sea turtle cells undergo intrinsic metabolic adjustments to cope with extreme oxygen fluctuations, aligning with the remarkable hypoxic tolerance exhibited by these animals, which can endure up to 7\u00a0h of\u00a0breath\u2010holding underwater.\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>Key points<\/jats:title>\nHypoxic sea turtle cells bypass the Crabtree effect and boost antioxidant defences.<\/jats:p><\/jats:list-item>\nHypoxia exposure fine\u2010tunes mitochondrial function in sea turtle cells.<\/jats:p><\/jats:list-item>\nPreserving mitochondrial architecture during hypoxia may help sea turtle cells restart respiration upon reoxygenation after extended hypoxia.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp288755","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T20:39:54Z","timestamp":1758746394000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypoxia exposure fine\u2010tunes mitochondrial function in sea turtle cells"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8942-9740","authenticated-orcid":false,"given":"B. Gabriela","family":"Arango","sequence":"first","affiliation":[{"name":"Department of Integrative Biology University of California Berkeley CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5554-1638","authenticated-orcid":false,"given":"David C.","family":"Ensminger","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences San Jose State University San Jose CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dianna","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology University of California Berkeley CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-6767","authenticated-orcid":false,"given":"C\u00e9line A.","family":"Godard\u2010Codding","sequence":"additional","affiliation":[{"name":"Department of Environmental Toxicology Texas Tech University Lubbock TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1014-5214","authenticated-orcid":false,"given":"Jos\u00e9 Pablo","family":"V\u00e1zquez\u2010Medina","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology University of California Berkeley CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"91","article-title":"Hypoxia exposure blunts angiogenic signaling and upregulates the antioxidant system in endothelial cells derived from elephant seals","volume":"22","author":"Allen K. 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