TRIM28 Is an E3 Ligase of IRP2 Suppressing Ischemia/Reperfusion-Induced Myocardial Ferroptosis - PubMed
4 days ago
- #ferroptosis
- #ischemia/reperfusion
- #TRIM28
- TRIM28 acts as an E3 ligase targeting IRP2, suppressing ferroptosis in myocardial ischemia/reperfusion (I/R) injury.
- TRIM28 expression is downregulated in ferroptotic cardiomyocytes and I/R-injured hearts, while its overexpression protects against ferroptosis.
- Mechanistically, TRIM28 promotes K48-linked ubiquitination of IRP2 at K877, reducing IRP2 and TFR1 levels, thereby lowering iron uptake and ferroptosis.
- p55γ interacts with and upregulates TRIM28, mitigating I/R-induced ferroptosis.
- Perhexiline inhibits myocardial ferroptosis by upregulating p55γ and TRIM28.
- Human ischemic heart disease samples show decreased TRIM28 and p55γ, but increased IRP2 and TFR1.