The hippo-YAP1/TEAD1-SLC7A5 axis: uncovering a novel therapeutic target for oxalate-induced renal tubular ferroptosis - PubMed
5 hours ago
- #Hippo pathway
- #oxalate nephropathy
- #ferroptosis
- The study investigates the regulatory mechanisms of ferroptosis in renal tubular epithelial cells under high oxalate stress.
- High oxalate induces ferroptosis and activates the Hippo pathway, leading to YAP1 phosphorylation and inactivation.
- Multi-omics approaches identified YAP1 as a key regulator and SLC7A5 as its direct transcriptional target via TEAD1.
- High oxalate disrupts YAP1/TEAD1 binding to the SLC7A5 promoter, downregulating SLC7A5, which mediates ferroptosis under YAP1 inhibition.
- SLC7A5 downregulation restricts leucine availability and suppresses mTOR signaling, while leucine supplementation or mTOR reactivation reverses ferroptosis.
- The Hippo-YAP1/TEAD1-SLC7A5 axis is established as a master regulatory pathway for oxalate-induced ferroptosis, offering a therapeutic target for oxalate nephropathy.