A new study by Queen’s University doctoral candidate Brittany Edgett (Kinesiology and Health Studies) has found that exercise and fasting do not change the cellular location of a key enzyme involved in energy production – SIRT3 – as had been predicted in previous models.

The findings suggest that SIRT3 is not regulated by changes in its location within the cell and shed light on the role SIRT3 could play in energy production in human muscle tissue.

“Understanding how proteins like SIRT3 are regulated may be beneficial for individuals with metabolic disease,” Ms. Edgett says. “However, before we can start targeting these proteins, we have to know how they’re regulated in humans and how to control their function, which was the aim of this study.”

SIRT3 is an important enzyme involved in fat metabolism and energy production. Located within the mitochondria of human skeletal muscle, it acts by targeting specific enzymes and altering their activity.

Exercise and fasting have been shown to alter factors that regulate SIRT3 in animal models. To determine if these mechanisms occur in humans, healthy young men were split into two groups with one performing endurance exercise for an hour and the other fasting for 48 hours. The researchers then took skeletal muscle biopsies at various time points before and after exercise and fasting.

They found that, although the level of SIRT3 mRNA in cells decreases, its location does not change, suggesting that its activity is not regulated by changes in its abundance within mitochondria in human skeletal muscle.

Ms. Edgett says that the finding differs from what they expected based on previous findings in isolated cells. In demonstrating that the SIRT3 enzyme is not regulated in this way, researchers will be better able to understand the function and regulation of this protein in humans.

“It’s really important to confirm that these mechanisms actually occur in humans and if it’s worth targeting a specific protein in the future if researchers are attempting to design drugs or discover natural compounds that target these enzymes or pathways for the treatment and/or prevention of disease,” Ms. Edgett says.

The full study, which was published in the journal Experimental Physiology, can be found online.