Crabtree effect in kidney proximal tubule cells via late-stage glycolytic intermediates

Manjula Darshi, Jana Tumova, Afaf Saliba, Jiwan Kim, Judy Baek, Subramaniam Pennathur, Kumar Sharma

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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, mimicking the Crabtree effect. Studies in diabetic mice indicated a pattern of increased late-stage glycolytic intermediates consistent with a similar pattern occurring in vivo. Our results show the unique presence of the Crabtree effect in kidney PTEC and identify the major mediators of this effect.

Original languageEnglish (US)
Article number106462
JournaliScience
Volume26
Issue number4
DOIs
StatePublished - Apr 21 2023

Keywords

  • Biochemistry
  • Cell biology
  • Physiology

ASJC Scopus subject areas

  • General

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