iBRIC-inStem study revealed the role of Ubp3 in the Crabtree/ Warburg Effects of suppressing mitochondrial activity in high glucose environment
The latest study from Dr Sunil Laxman Lab explores why cells tend to suppress mitochondrial activity when exposed to high levels of glucose. This phenomenon is seen in the form of the Crabtree effect in yeast cells and the Warburg effect in cancer cells. In both these scenarios, the cells adopt the quickest way to generate energy (ATP) in order to proliferate at a rapid pace (fermentation in yeast and lactate production in cancer cells). The researchers found that a protein called Ubp3 helps control this switch. When cells don’t have Ubp3, their mitochondria stay active even with plenty of glucose. This happens because these cells change the way they process glucose, freeing up a key molecule called inorganic phosphate (Pi), which mitochondria need to work. Normally, cells use up Pi during glucose processing, limiting what’s available for the mitochondria. By adjusting Pi levels, cells can regulate mitochondrial activity. These findings highlight how the balance between glycolysis and Pi availability is a key factor in controlling mitochondrial function in high glucose conditions.
Vengayil V, Niphadkar S, Adhikary S, Varahan S, Laxman S. The deubiquitinase Ubp3/Usp10 constrains glucose-mediated mitochondrial repression via phosphate budgeting. Dang W, Isales C, eds. eLife. 2024;12:RP90293. doi:10.7554/eLife.90293
