WEHI Researchers Discover Ubiquitin Regulates Glycogen Storage Overturning Decades of Established Biological Theory

WEHI scientists find that ubiquitin tags glycogen for removal, a breakthrough that could lead to new treatments for diabetes and heart disease.

By: AXL Media

Published: Apr 24, 2026, 6:33 AM EDT

Source: Information for this report was sourced from EurekAlert!

Rewriting the Fundamentals of Sugar Metabolism

For generations, the pathway of glycogen metabolism has been considered a settled chapter in medical textbooks, taught to students as a well-defined biochemical process. However, a research team at the Walter and Eliza Hall Institute (WEHI) has uncovered a previously invisible mechanism that challenges this long-standing knowledge. Professor David Komander, head of WEHI’s Ubiquitin Signalling Division, stated that the team has identified a second pathway where stored sugar is directly regulated, likely on demand. This discovery suggests that biology books will need to be amended to reflect this new understanding of how the human body manages its energy reserves.

The Unconventional Role of Ubiquitin

Ubiquitin has long been recognized by scientists as a critical protein that "tags" damaged or unnecessary proteins to be recycled or removed from the body. Traditionally, it was believed that ubiquitin interacted exclusively with proteins; however, this new study demonstrates that it also attaches to glycogen, which is a sugar. Dr. Simon Cobbold, a co-lead author, noted that ubiquitin has been an unsung hero working quietly in the background to maintain life. By proving that this "tagging" system extends to sugars in both animal models and human cells, the research opens an entirely new frontier in the study of metabolic signaling.

Pioneering Technology Reveals Hidden Molecules

The breakthrough was made possible through a cutting-edge laboratory technique called NoPro-clipping, developed by the WEHI team over the last four years. This method allows researchers to use mass spectrometry to detect ubiquitination events that do not involve proteins, a process that was previously impossible to observe. First author Marco Jochem explained that the real strength of this tool is its versatility, as it has also uncovered ubiquitinated metabolites like glycerol and spermine within cells. Without this specific technological innovation, the remarkable interaction between ubiquitin and sugar would have remained hidden from the scientific community.