Discovery-driven research leads to breakthrough in understanding rare Sengers syndrome

July 14, 2017 by Kathryn Powley
Credit: University of Melbourne

Melbourne researchers have unlocked important information that could lead to improved treatment of a rare and serious genetic condition.

Sengers syndrome is a genetic mitochondrial disease. Most children born with it die as babies, but a milder form of the disease also exists with some people surviving for multiple decades.

The new research, which involved a collaboration between the University of Melbourne's Bio21 Institute, the Murdoch Childrens Research Institute, Monash University and La Trobe University, uncovered an unexpected link between the gene that causes Sengers syndrome, AGK, and a cellular process referred to as " transport".

Professor David Thorburn's team identified changes in the AGK gene as the cause of Sengers syndrome in 2012. However, it was unclear how the expected of AGK led to the abnormal mitochondrial function they found in the two Australian patients identified at that time. Subsequently another 30 patients have been described internationally, most of whom suffer from severe heart disease and cataracts.

Dr Diana Stojanovski investigated the inner workings of AGK and what she found could lead to improved treatments and therapies for the incurable condition.

Dr Stojanovski explains that the mitochondrion is an organelle found in all cells of our bodies and considered the "powerhouse" of the cell, where the food we eat is metabolised into energy to sustain life and organ function. When mitochondria don't function properly organs fail and people get sick.

Mitochondria is bound by a double membrane with "gate-keepers" or "carrier proteins" embedded in the inner membrane that regulate which molecules and metabolites can enter.

The molecules that pass through these gate-keepers are needed for various important processes, such as the metabolism of fats and proteins for energy.

"Inside the mitochondria you have a number of tiny molecular machines that are responsible for assembling these gate-keeper molecules so they can do their job," Dr Stojanovski says.

"This is a highly tuned process. When these machines have faulty parts, then it can have severe effects on our metabolism, like what we see in Sengers sydnrome."

Dr Stojanovski's team found the AGK belonged to a molecular machine known as TIM22, which organises tunnel-like carrier proteins into the inner membrane, which then transport molecules into and out of the organelle.

This function was crucial for various processes, including energy production.

"Until this discovery Sengers syndrome was believed to be a defect of lipid metabolism in cells," Dr Stojanovski says. "Our work is paradigm-shifting and suggests defects in the process of leads to the disease."

Explore further: Researchers sniff out potential Leigh syndrome treatment

Related Stories

Researchers sniff out potential Leigh syndrome treatment

July 18, 2016
A mouse with dysfunctional mitochondria may hold the key to treating Leigh syndrome in humans.

Unravelling the genetic mystery behind mitochondrial disease

September 15, 2016
Researchers from the Monash Biomedicine Discovery Institute in Melbourne have identified two new genes linked to a major cause of mitochondrial disease. Their research opens the way for better genetic diagnosis of the disease ...

Unraveling the mystery of DNA attacks in cells' powerhouse could pave way for new cancer treatments

April 28, 2017
New research has unravelled the mystery of how mitochondria—the energy generators within cells—can withstand attacks on their DNA from rogue molecules.

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.