{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T01:15:58Z","timestamp":1778980558273,"version":"3.51.4"},"reference-count":64,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Naked mole\u2010rats (NMRs; <jats:italic>Heterocephalus glaber<\/jats:italic>) are among the most hypoxia\u2010tolerant mammals. There is evidence that the NMR brain tolerates <jats:italic>in vitro<\/jats:italic> hypoxia and NMR brain mitochondria exhibit functional plasticity following <jats:italic>in vivo<\/jats:italic> hypoxia; however, if and how these organelles tolerate ischaemia and how ischaemic stress impacts mitochondrial energetics and redox regulation is entirely unknown. We hypothesized that mitochondria fundamentally contribute to <jats:italic>in vitro<\/jats:italic> ischaemia resistance in the NMR brain. To test this, we treated NMR and CD\u20101 mouse cortical brain sheets with an <jats:italic>in vitro<\/jats:italic> ischaemic mimic and evaluated mitochondrial respiration capacity and redox regulation following 15 or 30\u00a0min of ischaemia or ischaemia\/reperfusion (I\/R). We found that, relative to mice, the NMR brain largely retains mitochondrial function and redox balance post\u2010ischaemia and I\/R. Specifically: (i) ischaemia reduced complex I and II\u2010linked respiration \u223c50\u201370% in mice, <jats:italic>vs<\/jats:italic>. \u223c20\u201340% in NMR brain, (ii) NMR but not mouse brain maintained relatively steady respiration control ratios and robust mitochondrial membrane integrity, (iii) electron leakage post\u2010ischaemia was lesser in NMR than mouse brain and NMR brain retained higher coupling efficiency, and (iv) free radical generation during and following ischaemia and I\/R was lower from NMR brains than mice. Taken together, our results indicate that NMR brain mitochondria are more tolerant of ischaemia and I\/R than mice and retain respiratory capacity while avoiding redox derangements. Overall, these findings support the hypothesis that hypoxia\u2010tolerant NMR brain is also ischaemia\u2010tolerant and suggest that NMRs may be a natural model of ischaemia tolerance in which to investigate evolutionarily derived solutions to ischaemic pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Ischaemia is highly deleterious to the mammalian brain and this damage is largely mediated by mitochondrial dysfunction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Naked mole\u2010rats are among the most hypoxia\u2010tolerant mammals and their brain tolerates ischaemia <jats:italic>ex vivo<\/jats:italic>, but the impact of ischaemia on mitochondrial function is unknown.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Naked mole\u2010rat but not mouse brain mitochondria retain respiratory capacity and membrane integrity following ischaemia or ischaemia\/reperfusion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Differences in free radical management and respiratory pathway control between species may mediate this tolerance.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results help us understand how natural models of hypoxia tolerance also tolerate ischaemia in the brain.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp281942","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:04:36Z","timestamp":1630541076000},"page":"4671-4685","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Naked mole\u2010rat brain mitochondria tolerate <i>in vitro<\/i> ischaemia"],"prefix":"10.1113","volume":"599","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-640X","authenticated-orcid":false,"given":"Hang","family":"Cheng","sequence":"first","affiliation":[{"name":"Department 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