▎ACHIEVEMENTS

Intracellular organelles, bounded by biological membranes, reply on vesicle transport for nutrient exchange, signal transmission, material recycling, and waste processing—functions analogous to the circulatory system in the human body. Nearly a hundred genetic disorders, autoimmune diseases, and cancers have been linked to disruptions in vesicle transport.

A research team led by Prof. Fang-Jen Lee has demonstrated that intracellular glycerol regulates the localization and function of the Golgi structural protein Imh1, clarifying a molecular link between metabolism and vesicle transport. This significant research finding has been published in the prestigious international journal Nature Structural & Molecular Biology.

The Golgi apparatus is a central organelle in eukaryotic cells responsible for protein modification and vesicle trafficking; its integrity is essential for accurate cargo delivery to target organelles. Golgi transport defects can cause neurological decline, developmental disorders, autoimmune conditions, and cancer. Prof. Lee’s research group has focused on the molecular mechanisms governing Golgi vesicle transport; although prior research had found that Imh1 supports Golgi structure and transport, the precise regulation mechanism remained unresolved.

This research was the first to discover that when cells encounter hypotonic shock and intracellular glycerol levels decrease, the localization of Imh1 and the integrity of the Golgi apparatus are disrupted. Furthermore, the research confirmed that metabolic perturbations that reduce glycerol levels prevent correct Imh1 targeting to the Golgi, resulting in transport dysfunction. To uncover the molecular basis of this regulation, Prof. Lee collaborated with Prof. Chia-Jung Yu's proteomics group at Chang Gung University. They used isotope-labeled cross-linkers and cross-linking mass spectrometry (XL-MS) to quantify changes at lysine cross-linking sites, demonstrating that it is glycerol that alters Imh1’s conformation. Importantly, the regulatory mechanism operates in both yeast and mammalian cells, indicating evolutionary conservation.

Because glycerol is a central metabolic intermediate, these results reveal a previously underappreciated connection between intracellular metabolism and vesicle transport pathways, highlighting how metabolic state influences intracellular trafficking. “Intracellular glycerol levels might be associated with various vesicle transport diseases, making the exploration of its mechanisms potentially valuable for discovering new therapeutic strategies with clinical applications,” remarked Prof. Fang-Jen S. Lee.