In the normal kidney, the Na+/H+ exchanger NHE1 interacts with phosphatidylinositol 4,5-bisphosphate—PI(4,5)P2—to maintain proximal tubule cell survival. However, research in mouse models has shown that glomerular injury leads to long-chain acetyl-CoA infiltration, which competes with PI(4,5)P2 for NHE1 binding and stimulates lipoapoptosis. Inhibition of long-chain acetyl-CoA synthesis in the proximal tubule protected these cells from apoptosis. Overall, the data suggest that the NHE1–PI(4,5)P2 interaction is disturbed in albuminuria and lipiduria via a reduced apoptotic threshold.
References
Khan, S. et al. Lipotoxic disruption of NHE1 interaction with PI(4,5)P2 expedites proximal tubule apoptosis. J. Clin. Invest. 10.1172/JCI71863
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Lipotoxicity dysregulates NHE1 function, causes apoptosis. Nat Rev Nephrol 10, 240 (2014). https://doi.org/10.1038/nrneph.2014.42
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DOI: https://doi.org/10.1038/nrneph.2014.42