Mitochondria from anoxia-tolerant animals reveal common strategies to survive without oxygen

The mitochondrion plays a critical role in the development of Oxygen (O-2)-related diseases. While research has predominantly focused on hypoxia-sensitive mammals as surrogates for humans, the use of animals which have naturally evolved anoxia tolerance has been largely ignored. Remarkably, some animals can live in the complete absence of O-2 for days, months and even years, but surprisingly little is currently known about mitochondrial function in these species. In contrast to mammals, mitochondrial function in anoxia-tolerant animals is relatively insensitive to in vitro anoxia and reoxygenation, suggesting that anoxia tolerance transcends to the level of the mitochondria. Furthermore, long-term anoxia is associated with marked changes in the intrinsic properties of the mitochondria from these species, which may afford protection against anoxia-related damage. In the present review, we highlight some of the strategies anoxia-tolerant animals possess to preserve mitochondrial function in the absence of O-2. Specifically, we review mitochondrial Ca2+ regulation, proton leak, redox signaling and mitochondrial permeability transition, in phylogenetically diverse groups of anoxia-tolerant animals. From the strategies they employ, these species emerge as model organisms to illuminate novel interventions to mitigate O-2-related mitochondrial dysfunction in humans.