Small plants swim inside our cells and provide them with almost all the energy they need: mitochondria. Their effectiveness decreases as we age, but also when we encounter many diseases such as diabetes, cancer or Parkinson̵7;s. This is why scientists are increasingly interested in how they work. At the EPFL, a team has developed a protocol to measure their activity in live animals. Described in Chemical Biology of Nature, the method relies on the molecule responsible for firefly bioluminescence. In the truest sense of the word, this study sheds light on how mitochondria work.
Mitochondria are almost like cells within a cell. Like their host, they have a membrane that protects their genetic material and, above all, filter exchanges with the outside. The difference in electrical charge between the inside and outside of the mitochondria, called the ‘membrane potential’, allows certain molecules to pass through while others grip the breast.
While between the two poles of a used electric battery, the membrane potential of the mitochondria can sometimes drop. To scientists, this is an incomprehensible key that its functions are impaired.
We know how to measure the phenomenon in cultured cells. But so far, you can not really see it in live animals. “Cell cultures are not very effective in studying myochondria-related diseases,” explains Elena Goun, EPFL professor and lead author of the article. “Cancer or diabetes involve complex exchanges between different cell types, so we need animal models.” “.
Elena Goun and her colleagues have found a way to study the phenomenon in live rats. They use animals that have been genetically modified to express luciferase – an enzyme that produces light when combined with another compound called luciferin. This is how fire flames sometimes light up our summer evenings.
Scientists have developed two molecules that, when injected into rodents, pass into the mitochondria, where they activate a chemical reaction. Mychondria then produces luciferin and flushes it out. Luciferine combines with luciferase in mouse cells and produces light.
“In a completely darkened room, you can see rats glowing, just like fireflies,” says Elena Goun.
Researchers only need to measure the intensity of light to get a clear picture of how mitochondria work. When they function less, their membrane allows for fewer chemical compounds. Luciferine production decreases, and hence brightness.
To demonstrate the potential of their method, the researchers conducted several experiments. For example, they observed that older rodents produce significantly less light. This decrease in light reflects a decrease in the activity of mitochondria potential their membrane potential is much lower than in young rodents. We know that age causes a decrease in mitochondrial activity, but this is the first time the phenomenon has been accurately measured directly in live animals.
The team also tested a chemical known to rejuvenate mitochondria: nicotinamide ribosides. This molecule is non-toxic and commercially available as a dietary supplement. Mice given this complex produced more light, a sign of increased mitochondrial activity.
The researchers were also able to measure the same phenomenon in animal models of cancer. This can be a great help for researching anticancer drugs. In addition, they also successfully demonstrated monitoring of mitochondrial membrane potential in mitochondrial-rich brown adipose tissue cells. Stimulating it can help cure certain forms of overweight.
The method described by Elena Goun is primarily intended for scientists who want to better understand the role of mitochondria and who need an animal model. The field of application is wide: diabetes, oncology, aging, food, neurogenetic diseases … “Our process can measure different degrees of mitochondrial activity, and not just an on / off signal,” explains Elena Goun. “Extremely sensitive – much more than an affordable and easy PET scan.
Lysosome communication in the mitochondria regulates longevity
Bazhin, AA, Sinisi, R., De Marchi, U. et al. A bioluminescent probe for longitudinal monitoring of mitochondrial membrane potential. Nat Chem Biol (2020). doi.org/10.1038/s41589-020-0602-1
Provided by the Ecole Polytechnique Federale de Lausanne
citation: Fireflies shed light on mitochondria function (2020, August 10) Retrieved 11 August 2020 from https://phys.org/news/2020-08-fireflies-function-mitochondria.html
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