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

Abstract

AimIn 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.MethodsHere, 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).ResultsWe 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.ConclusionOur 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.