biostudies-literatureDarshi MNational Center for Advancing Translational SciencesJuvenile Diabetes Research Foundation United States of AmericaNCATS NIH HHSNIDDK NIH HHSThe University of Texas Health Science Center at San AntonioNational Institutes of HealthU.S. Department of Veterans AffairsNIGMS NIH HHS106462https://www.ebi.ac.uk/biostudies/studies/S-EPMC10119590biostudies-literatureUnknown26(4)The Crabtree effect is defined as a rapid glucose-induced repression of mitochondrial oxidative metabolism and has been described in yeasts and tumor cells. Using plate-based respirometry, we identified the Crabtree effect in normal (non-tumor) kidney proximal tubule epithelial cells (PTEC) but not in other kidney cells (podocytes or mesangial cells) or mammalian cells (C2C12 myoblasts). Glucose-induced repression of respiration was prevented by reducing glycolysis at the proximal step with 2-deoxyglucose and partially reversed by pyruvate. The late-stage glycolytic intermediates glyceraldehyde 3-phosphate, 3-phosphoglycerate, and phosphoenolpyruvate, but not the early-stage glycolytic intermediates or lactate, inhibited respiration in permeabilized PTEC and kidney cortex mitochondria, mimiScienceCrabtree effect in kidney proximal tubule cells via late-stage glycolytic intermediates.PMC10119590P30 DK089503P30 DK0819435F30DK121463T32 GM007863P30 DK89503TL1 TR002647R24DK082841Saliba ADarshi MTumova JBaek JPennathur SKim JSharma KfalseCrabtree effect in kidney proximal tubule cells via late-stage glycolytic intermediates.The Crabtree effect is defined as a rapid glucose-induced repression of mitochondrial oxidative metabolism and has been described in yeasts and tumor cells. Using plate-based respirometry, we identified the Crabtree effect in normal (non-tumor) kidney proximal tubule epithelial cells (PTEC) but not in other kidney cells (podocytes or mesangial cells) or mammalian cells (C2C12 myoblasts). Glucose-induced repression of respiration was prevented by reducing glycolysis at the proximal step with 2-deoxyglucose and partially reversed by pyruvate. The late-stage glycolytic intermediates glyceraldehyde 3-phosphate, 3-phosphoglycerate, and phosphoenolpyruvate, but not the early-stage glycolytic intermediates or lactate, inhibited respiration in permeabilized PTEC and kidney cortex mitochondria, mim2023-01-01T00:00:00Z2023 Apr2026-05-28T16:50:42.923Z2025-02-19T04:16:03.698ZS-EPMC101195903709123910.1016/j.isci.2023.106462