Autor: |
Manjula Darshi, Jana Tumova, Afaf Saliba, Jiwan Kim, Judy Baek, Subramaniam Pennathur, Kumar Sharma |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
iScience, Vol 26, Iss 4, Pp 106462- (2023) |
Druh dokumentu: |
article |
ISSN: |
2589-0042 |
DOI: |
10.1016/j.isci.2023.106462 |
Popis: |
Summary: 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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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