Publication Date

9-24-2025

Document Type

Article

Publication Title

Journal of Physiology

DOI

10.1113/JP288755

Abstract

Abstract: Sea turtles experience extreme fluctuations in oxygen levels derived from extended breath-hold 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-α when exposed to chemical or environmental hypoxia. In contrast to lizard cells, sea turtle cells exhibit a faster and more robust response to 1 h or 24 h of hypoxia exposure (0.1% O2), 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 h 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 h of breath-holding underwater. (Figure presented.). Key points: Hypoxic sea turtle cells bypass the Crabtree effect and boost antioxidant defences. Hypoxia exposure fine-tunes mitochondrial function in sea turtle cells. Preserving mitochondrial architecture during hypoxia may help sea turtle cells restart respiration upon reoxygenation after extended hypoxia.

Funding Sponsor

Ford Foundation

Keywords

cellular respiration, diving, metabolomics, oxidative stress, reptiles

Comments

This is the peer reviewed version of the following article:Arango, B.G., Ensminger, D.C., Xing, D., Godard-Codding, C.A. and Vázquez-Medina, J.P. (2026), Hypoxia exposure fine-tunes mitochondrial function in sea turtle cells. J Physiol. https://doi.org/10.1113/JP288755, which has been published in final form at https://doi.org/10.1113/JP288755. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

Department

Biological Sciences

Available for download on Thursday, September 24, 2026

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