TORC1 controls the normal growth of cells, but when too active it can promote diseases. A new study led by biologists from the University of Geneva and published in Nature yesterday describes how the activity of TORC1 is regulated.
In the presence of sugar, individual TORC1s stimulate the various metabolic processes that allow cells to grow. In the absence of sugar, TORC1s assemble into a tubular structure, rendering them inactive and thus cell growth stops. The formation and disassembly of these tubules are easy to observe in living cells, which, in future work, would make it possible to identify compounds that interfere with this process. As regulators of cellular growth, such compounds would represent an interesting anti-cancer strategy, according to the research team.
TORC1 is hyperactive in several diseases, including cancer. Cancer cells massively upregulate growth pathways, and are thus particularly sensitive to the presence of sugar. In this study, the team sought to understand how sugar regulates the activity of TORC1.
With help from researchers from the University of Auckland and the École Polytechnique Fédérale de Lausanne, the appearance of a new TORC1 structure in cells was revealed. "When cells are deprived of glucose, individual TORC1s assemble together to form a tubular structure that can reach one-fifth of the size of the cell. Formation of this tubule, which we call a TOROID, allows both the storage and inactivation of TORC1 which halts cell growth," explains Manoël Prouteau, a member of the Geneva group and first author of the article.
The study also showed that the re-addition of glucose causes the rapid disassembly of TOROIDs, allowing cells to resume their growth with the subsequent reactivation of liberated TORC1s. "This work has been done in yeast; indeed, many of the discoveries related to TOR have been made in yeast before being confirmed in mammals. It is therefore very likely that TOROIDs exist and function in the same way in humans," notes Robbie Loewith, director of the department of molecular biology of the University of Geneva Faculty of Sciences.
The assembly and disassembly of TOROIDs, the largest protein helix discovered to date, can be easily observed thanks to advances in microscopy methods. This will make it possible to search for compounds that can stabilize or destabilize them, inside cells. Such compounds would be of great clinical interest as modifiers of cell growth.
Image: A formation and disassembly of TOROIDs. Image courtesy of UNIGE.