Nav: Home

Fireflies shed light on the function of mitochondria

August 10, 2020

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, but also when we face many diseases such as diabetes, cancer or Parkinson's. This is why scientists are increasingly interested in how they work. At EPFL, a team has developed a protocol to measure their activity live in living animals. Described in Nature Chemical Biology, the method relies on the molecule responsible for the firefly's bioluminescence. In the most literal sense of the word, this study sheds light on how mitochondria work.

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 other ramain 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. "Cell cultures are not very effective in studying diseases linked to mitochondria", explains Elena Goun, professor at EPFL and lead author of the article: "Cancer or diabetes involve complex exchanges between various types of cells, therefore we need animal models. "

Elena Goun and her colleagues 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 the mice's cells and produce light.

"In a completely darkened room, you can see the mice glowing, just like fireflies," says Elena Goun.

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. We know that age causes a decrease in the activity of mitochondria, but this is the first time that the phenomenon has been accurately measured directly in living animals.

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.

The researchers were also able to measure the same phenomenon in animal models of cancer. This could be of great help for anticancer drug research. In addition, they also successfully demonstrated monitoring of mitochondria membrane potential in cells of brown adipose tissue, rich in mitochondria. Its stimulation could help cure certain forms of obesity.

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, nutrition, neurogenerative diseases... "Our process can measure varying degrees of mitochondria activity, and not just an on / off signal", explains Elena Goun. "It is extremely sensitive - much more than a PET scan - affordable and easy to implement.
-end-


Ecole Polytechnique Fédérale de Lausanne

Related Diabetes Articles:

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.
Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.
Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).
Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.
Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.
Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.
Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
More Diabetes News and Diabetes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Sound And Silence
Sound surrounds us, from cacophony even to silence. But depending on how we hear, the world can be a different auditory experience for each of us. This hour, TED speakers explore the science of sound. Guests on the show include NPR All Things Considered host Mary Louise Kelly, neuroscientist Jim Hudspeth, writer Rebecca Knill, and sound designer Dallas Taylor.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

Kittens Kick The Giggly Blue Robot All Summer
With the recent passing of Ruth Bader Ginsburg, there's been a lot of debate about how much power the Supreme Court should really have. We think of the Supreme Court justices as all-powerful beings, issuing momentous rulings from on high. But they haven't always been so, you know, supreme. On this episode, we go all the way back to the case that, in a lot of ways, started it all.  Support Radiolab by becoming a member today at Radiolab.org/donate.