You probably do not think much about what happens to sugar in your body after a meal. But researchers at Australia’s WEHI have uncovered a mechanism that could significantly change how scientists understand the way the body stores and manages sugar reserves.
The discovery centers on glycogen, the form in which your body stores sugar for later use. This is not the same as the sugar circulating in your bloodstream. Glycogen is more like an energy backup system, stored mainly in the liver and muscles and ready to be tapped between meals.
A Cellular Tag Scientists Have Known for Decades Has a New Job
At the center of the discovery is ubiquitin, a small protein that works a bit like a molecular label inside the cell. Scientists have long known it mainly for its role in marking proteins, for example when a cell needs to flag damaged or unnecessary proteins so they can be broken down and recycled.
But the new study shows that ubiquitin does not attach only to proteins. Researchers found that it can also bind directly to glycogen. That is the surprising part: glycogen is not a protein. It is a sugar. The finding expands a textbook idea that biology has treated as largely settled for decades.
“It’s quite likely biology books will need to be amended as a result of our findings,” Prof. Komander said. “We’ve uncovered a second pathway where glycogen can be directly regulated – likely on demand.”
The findings were published in the journal Nature, which makes clear this is not just a minor laboratory curiosity. The study raises a bigger question: has the body been using ubiquitin as a broader control tool than scientists realized?
Too Much Glycogen Can Be Dangerous. Researchers Want to Target Sugar Stores Directly
Glycogen itself is not the enemy. Your body needs it as an energy reserve. The problem begins when too much of it builds up in cells, or when the body cannot break it down properly. At that point, something useful can become a burden. Excess glycogen has been linked to diabetes, obesity, heart disease, and liver disease.
There is also a group of rare inherited conditions known as Glycogen Storage Diseases. In these disorders, the body cannot properly make or break down glycogen, so it may accumulate in tissues where it causes damage. For a non-specialist, the simplest way to picture it is as an energy warehouse that keeps filling up while the body cannot properly take supplies back out.
Most current treatments do not directly target glycogen itself. Even modern drugs such as Ozempic affect blood sugar more indirectly, through hormonal pathways that influence appetite, insulin, and metabolism. What makes this discovery interesting is that it points to a deeper possibility: intervening directly in the stored form of sugar.
“Without being able to regulate glycogen itself, it is hard to combat its accumulation – the root cause of many diseases. That’s why our study is exciting. We’ve found a way to go straight to the source,” Prof. Komander said.
The New NoPro-Clipping Technique Revealed How Ubiquitin Attaches to Glycogen
The discovery was possible because of a new technique called NoPro-clipping, which the research team developed over four years. The method allows scientists to detect ubiquitin attached to non-protein molecules using mass spectrometry. In plain terms, it gives researchers a way to see molecular changes that were previously almost invisible.
“Not only can we use it to detect ubiquitinated glycogen – we can also uncover ubiquitinated metabolites like glycerol and spermine, which we’ve discovered for the first time in all our cells,” lead author and doctoral candidate Marco Jochem said.
Without this method, the process would probably have remained hidden. Earlier techniques in the ubiquitin field were built mainly to study proteins, which meant they could miss this entire layer of cellular regulation.
During Fasting, the Body Burns Through Glycogen. That Is When Ubiquitin Tags Rose
One of the most striking parts of the study came from experiments in mice. The researchers tracked how ubiquitin attached to glycogen in the liver during feeding and fasting. The liver matters here because it acts like a major energy storage site. After a meal, when the body has enough sugar, some of that energy is stored as glycogen. In the absence of food, the body begins tapping into those reserves.
The team noticed something important. When mice were fasting and needed energy, glycogen levels in the liver dropped. At the same time, ubiquitin tags increased on the glycogen that remained. In other words, the more the body reached into its sugar reserves, the more visible this molecular tag became.
That suggests ubiquitin may be part of the machinery that controls glycogen breakdown. It may not be just a passive marker appearing in the background, but part of a system that helps the cell decide what to do with stored sugar. Put simply, the body may not only store and spend glycogen. It may also label it so cells know how to handle it.
Lowering Glycogen in Cells Could Point to a New Treatment Direction
The researchers took another important step. When they increased glycogen ubiquitination in cells, glycogen levels went down. That means they were not simply observing an unusual label on stored sugar. They also showed that when this label becomes more abundant, the cell may process glycogen differently and reduce how much of it remains.
That is why the finding matters from a medical point of view. This is not a finished drug, and it is not a therapy that could be given to patients tomorrow. But it does point to a new direction: diseases driven by excessive glycogen storage may one day be tackled closer to the source of the problem.
This could be especially important for people with Glycogen Storage Diseases, where the body cannot properly make or break down stored sugar. Glycogen can then accumulate in the liver, muscles, or other tissues and cause serious health problems. If scientists can learn how to safely influence this process, it could open an entirely new area of treatment.
“Ubiquitin is really an unsung hero that has been quietly working in the background all this time, keeping us alive,” Dr. Simon Cobbold said.
Ubiquitin on Glycogen May Not Be the Only Surprise. Scientists Found Tags on Other Molecules Too
The discovery does not stop with glycogen. The researchers also detected ubiquitin attached to other non-protein molecules, including glycerol and spermine. That matters because these molecules are not proteins either. It suggests ubiquitin may have a much broader role in the cell than scientists previously assumed.
In other words, the researchers may have opened the door to a part of cell regulation that existing methods simply could not see. If ubiquitin is a tag the cell uses to mark important molecules, this study suggests that tag does not belong only on proteins. It may also appear on molecules involved in metabolism and the everyday chemical work that keeps cells running.
Jochem said glycogen may only be the beginning:
“Our discovery is rewriting the fundamental rules of biology and ubiquitin signalling. And I’m sure we’ve only hit the tip of the iceberg.”
According to WEHI, the researchers have already begun early discussions with investors about how the findings could eventually be used in practice. For now, caution is needed. There is a long road between a discovery in cells and a medicine for patients. But if scientists can better understand and safely control this mechanism, it could lead to a completely new class of treatments for diseases in which the body stores or breaks down glycogen incorrectly.
