One of my favorite things about science fiction is when the genre takes inspiration from the natural world. For example, tales involving deep-space travel often begin with the protagonist awakening from a hibernation-like state – allowing them to get around the problem of aging as they traverse the stars. Here on Earth, some mammals use hibernation to decrease their metabolism to near-undetectable levels, which helps them survive low temperatures and lack of food during winter seasons. Achieving this kind of metabolic stasis in addition to prolonging survival after trauma are just two of the many important applications that studying hibernation could provide.
One key to understanding how hibernators – such as the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) – lower their metabolism is to study how they adjust their mitochondria, as these organelles provide most of the energy (in the form of ATP) required for life and cellular activity. Until recently, it was believed that mitochondrial enzymes produce ATP by passing electrons around as they randomly collide into each other. But Amalie Hutchinson and colleagues from the University of Western Ontario in Canada wanted to understand whether these enzymes were consistently bound together – known as supercomplexing – and whether these associations change between seasons and as these animals lower their metabolism when they hibernate.
The team captured thirteen-lined ground squirrels in Carman, MB, Canada, and brought them back to their lab in London, ON, Canada, where they were housed under conditions simulating summer temperatures (∼21°C) and natural day length in Carman. As winter approached, the scientists lowered the environmental temperature to 4°C and shortened the day length to 1 h light and 23 h dark to simulate winter hibernation conditions. They also collected mitochondria from the heart, liver and brown adipose tissue – which uses mitochondria to generate warmth – at three time points: summer, when the animals were active; when the animals had briefly arisen and were active during the winter hibernation; and during winter hibernation. The researchers then measured the amounts of supercomplexes and their protein make-up using techniques that separate mitochondrial enzymes but leave supercomplexes intact.
The scientists found that rather than changing the total amount of supercomplexes between seasons or winter conditions these squirrels seem to shuttle one specific mitochondrial enzyme (complex III, which is a massive protein made up of 11 subunits) between larger and smaller supercomplexes. As these squirrels transitioned from being active in the winter to resuming hibernation, the amount of complex III in larger supercomplexes decreased in brown adipose tissue – which may be important for rapidly lowering their metabolism. In contrast, the amount of complex III in larger supercomplexes was greatest in the liver in winter, while complex III was more associated with smaller supercomplexes in the heart in the summer. These changes in heart and liver mitochondria could represent an important part of the seasonal changes in the metabolism of these animals.
Hutchinson and colleagues have shown that something as remarkable as completely shutting down your metabolism could involve very subtle changes in mitochondrial supercomplexes. That said, it's probably going to be a while before we can use the lessons learned from these squirrels to safely send people into deep space. In the meantime, much remains to be learned about how these hibernators signal these shifts in enzyme interactions and their ultimate effects on mitochondrial function.
