Researchers here demonstrate a way to visualize mitochondrial membrane potential, a measure of mitochondrial function, in living animals. A tailored genetic modification causes luciferase activity to correlate with mitochondrial membrane potential: engineered mice with better functioning mitochondria glow more brightly. This, in principle, allows for rapid testing of approaches that will restore mitochondrial function in old mice.
Tiny factories float inside our cells and provide them with almost all the energy they need: the mitochondria. Their effectiveness decreases when we get older. Mitochondria are almost like cells within the cell. Like their host, they have a membrane that protects their genetic material and, above all, filters exchanges with the outside. The difference in electrical charge between the inside and the outside of the mitochondria, called “membrane potential”, allow certain molecules to go through, while others remain at bay. As between the two poles of a used electric battery, the membrane potential of the mitochondria can sometimes drop. For scientists, this is an unmistakable clue that its functions are impaired.
We know how to measure the phenomenon on cultured cells. But until now, you couldn’t really see it on live animals. Now researchers have found a way to study the phenomenon in live mice. They use animals that are genetically modified to express luciferase – an enzyme that produces light when combined with another compound called luciferin. This is how fireflies sometimes light up our summer evenings. Scientists have developed two molecules that, when injected into the rodent, pass into the mitochondria, where they activate a chemical reaction. The mitochondria then produce luciferin and eject it outwards. Luciferin combines with luciferase in mouse cells to produce light.
Researchers need only measure light intensity to get a clear picture of how well the mitochondria are functioning. When they function less well, their membrane lets in less chemical compounds. The production of luciferin decreases, and therefore the luminosity too. To demonstrate the potential of their method, the researchers carried out several experiments. For example, they observed that older rodents produce significantly less light. This drop in light reflects a drop in the activity of mitochondria – their membrane potential is much lower than in younger rodents. The team also tested a chemical known to rejuvenate mitochondria: nicotinamide riboside. This molecule is non-toxic and commercially available as a dietary supplement. Mice given this compound produced more light, a sign of increased mitochondrial activity.