Heart mitochondria from naked mole-rats (Heterocephalus glaber) are more coupled, but similarly susceptible to anoxia-reoxygenation stress than in laboratory mice (Mus musculus)

Abstract

Naked mole-rats (Heterocephalus glaber; NMRs) are among the most hypoxia-tolerant mammals described to date and exhibit plastic responses during hypoxia exposure. The goal of the present study was to determine if heart mitochondria from NMRs functionally differ from those of hypoxia-intolerant common laboratory mice (Mus musculus). We assessed heart mitochondrial respiratory flux, proton leak kinetics, responses to in vitro anoxia-recovery, and maximal complex enzyme activities. When investigated at their respective body temperatures (28 °C for NMR and 37 °C for mice), NMR heart mitochondria had lower respiratory fluxes relative to mice, particularly for state 2 and oligomycin-induced state 4 leak respiration rates. When leak respiration rates were standardized to the same membrane potential, NMR mitochondria had lower complex II-stimulated state 2 respiration rates than mice. Both mice and NMRs responded similarly to an in vitro anoxia-recovery challenge and decreased state 3 respiration rate post-anoxia. Finally, NMRs had overall lower maximal complex enzyme activities compared with mice, but the magnitude of the difference did not correspond with observed differences in respiratory fluxes. Overall, heart mitochondria from NMRs appear more coupled than those of mice, but in both species the heart appears equally susceptible to ischemic-reperfusion injury.

Keywords: Enzyme activities; High resolution respirometry; Mitochondria; Mitochondrial membrane potential; Respiration flux.