Mechanical regulation of glycolysis: isoform-specific control of PFK1 in mechanotransduction

Cells in our bodies are constantly experiencing physical forces, for example, in the lungs during breathing or in the gut as food moves through. To handle these forces, cells need to stay strong and hold tightly to their neighbors. They do this using an internal support system called the cytoskeleton, which acts like a flexible scaffold. Strengthening this scaffold requires energy, which cells produce by breaking down sugar to generate a usable form of energy called ATP. However, it has not been clear how cells know when to make more energy in response to physical forces. In this research, we found that a protein called PFK1 helps connect these two processes. When cells are physically stressed, this protein becomes more active and helps increase energy production, while also interacting with the cell’s internal scaffold to help maintain strength. We also discovered that one specific form of this protein, called PFKM, is especially important for this response. Cells that lack PFKM are weaker and have trouble maintaining strong connections with neighboring cells under stress. Overall, this work shows how cells adjust their energy production to match physical demands, which helps tissues stay strong and function properly, and may provide insight into diseases where these processes do not work correctly.