Newly identified protein regulates lysosome positioning and cellular metabolism

Lysosomes are the control centers for the metabolism of cells and tissues, including the brain. They break down defective proteins and other macromolecules into their basic building blocks. At the same time, they determine whether a cell grows or switches into an energy-saving mode. In doing so, they play a key role in health and disease.

A research team led by Prof. Dr. Markus Damme of Bielefeld University and Prof. Volker Haucke, Director of the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), has now jointly elucidated a key mechanism underlying this regulation. “For the first time, we’re showing which protein turns off the central transport switch ARL8B,” says biochemist Markus Damme, who was recently appointed to Bielefeld University from Kiel. “This gives us a better understanding of how cells spatially organize their recycling centers - or, more specifically, their sustainability centers - and adapt them to nutrient deprivation,” adds Prof. Volker Haucke, who is the co-last author of the study alongside Markus Damme.

At the heart of this work, which was carried out through close collaboration between the teams led by Prof. Volker Haucke in Berlin and Prof. Markus Damme in Bielefeld, as well as researchers at Christian-Albrechts-Universität Kiel (CAU), is the protein ARL8B. It acts like a motor starter: when active, lysosomes travel along a cellular rail network - known as microtubules - to the cell periphery. There, they promote growth processes. Until now, however, it was unclear how this switch is turned off again.

The Bielefeld researchers identified the protein TBC1D9B as the crucial “off switch.” TBC1D9B binds to the lysosomal membrane protein TMEM55B and specifically inactivates ARL8B. Experts refer to this as a GAP function (GTPase‑activating protein), a mechanism that returns molecular switches to their inactive state.