The deubiquitinase Ubp3/Usp10 constrains glucose-mediated mitochondrial repression via phosphate budgeting

• DOI: 10.7554/elife.90293.2
• Publication Date: 2024-03-12T11:25:12Z
• Authors: Vineeth Vengayil; Shreyas Niphadkar; Swagata Adhikary; Sriram Varahan; Sunil Laxman
• Keywords: Derepression; Deubiquitinating enzyme

Many cells in high glucose repress mitochondrial respiration, as observed the Crabtree and Warburg effects. Our understanding of biochemical constraints for activation is limited. Using a Saccharomyces cerevisiae screen, we identified conserved deubiquitinase Ubp3 (Usp10), necessary repression. mutants have increased activity despite abundant glucose, along with decreased glycolytic enzymes, rewired metabolic network trehalose production. Utilizing Δubp3 cells, orthogonal approaches, establish that flux continuously consumes free Pi. This restricts access to inorganic phosphate (Pi), prevents activation. Contrastingly, metabolism enhanced production reduced GAPDH (as cells) restores collectively results Pi derepression, while restricting transport We therefore suggest glycolytic-flux dependent intracellular budgeting key constraint