Differential production of mitochondrial reactive oxygen species between mouse (Mus musculus) and crucian carp (Carassius carassius)

Aim

In most vertebrates, oxygen deprivation and subsequent re-oxygenation are associated with mitochondrial impairment and excess production of reactive oxygen species (ROS) like hydrogen peroxide (H₂O₂). This in turn triggers a cascade of cell-damaging events in a temperature-dependent manner. The crucian carp (Carassius carassius) is one of few vertebrates that survives months without oxygen at cold temperatures and overcomes oxidative damage during re-oxygenation periods. Mitochondria of this anoxia-tolerant species therefore serve as an excellent model in translational research to study adaptation and resilience to low oxygen conditions and thermal variability.

Methods

Here, we used high-resolution respirometry on isolated mitochondria from hearts of crucian carp and the anoxia-intolerant mouse (Mus musculus), at 37 and 8°C; two temperatures relevant for transplantation medicine (i.e., graft preservation and subsequent rewarming).

Results

We find: (1) a striking difference in H₂O₂ release between the two species at 37°C despite comparable mitochondrial efficiency and capacity, (2) a massive H₂O₂ release after inhibition of complex V in mouse at 37°C that is absent in crucian carp, and prevented in mouse by incubation at 8°C or uncoupling with a protonophore at 37°C, and (3) indications that differences in mitochondrial complex I and II capacity and thermal sensitivity influence the release of mitochondrial H₂O₂ relative to respiration.

Conclusion

Our findings provide comparative insights into a spectrum of mitochondrial adaptations in vertebrates and the importance of thermal variability. Furthermore, the species- and temperature-related changes associated with mitochondria highlighted in this study may help identify mitochondria-based targets for translational medicine.