biostudies-literatureUnknown228(15)Ojaghi MNatural Sciences and Engineering Research Council of CanadaUniversity of OttawaMost vertebrates upregulate anaerobic metabolism in severe hypoxia, which results in metabolic acidosis that must be resolved during reoxygenation. Naked mole-rats (NMRs) are hypoxia-tolerant mammals and drastically reduce their metabolic rate while maintaining systemic pH homeostasis during acute hypoxia. Whether NMRs employ anaerobic metabolism in hypoxia is currently debated. Given the robust systemic hypoxic hypometabolism of this species, we hypothesized that anaerobic metabolism is recruited on a tissue-specific basis that varies between developmental stages and colony caste position. To test this, we treated subordinate juvenile and adult, and breeding (queen) NMRs in normoxia (21% O2) or hypoxia (3% O2) for 1 h, and then measured blood lactate, glycolytic enzyme activity, and the eThe Journal of experimental biologyjeb250397https://www.ebi.ac.uk/biostudies/studies/S-EPMC12377813biostudies-literatureSevere acute hypoxia upregulates anaerobic metabolism in non-reproductive but not queen naked mole-rats.PMC12377813Pamenter MEOjaghi MfalseSevere acute hypoxia upregulates anaerobic metabolism in non-reproductive but not queen naked mole-rats.Most vertebrates upregulate anaerobic metabolism in severe hypoxia, which results in metabolic acidosis that must be resolved during reoxygenation. Naked mole-rats (NMRs) are hypoxia-tolerant mammals and drastically reduce their metabolic rate while maintaining systemic pH homeostasis during acute hypoxia. Whether NMRs employ anaerobic metabolism in hypoxia is currently debated. Given the robust systemic hypoxic hypometabolism of this species, we hypothesized that anaerobic metabolism is recruited on a tissue-specific basis that varies between developmental stages and colony caste position. To test this, we treated subordinate juvenile and adult, and breeding (queen) NMRs in normoxia (21% O2) or hypoxia (3% O2) for 1 h, and then measured blood lactate, glycolytic enzyme activity, and the e2025-01-01T00:00:00Z2025 Aug2026-05-10T01:51:15Z2026-04-08T01:25:32.642ZS-EPMC123778134058354610.1242/jeb.250397