IFI16 is essential to linking DNA damage and ferroptosis in acute kidney injury - PubMed
4 hours ago
- #DNA Damage
- #Acute Kidney Injury
- #Ferroptosis
- IFI16 plays a critical role in linking DNA damage to ferroptosis in acute kidney injury (AKI).
- Levels of IFI16 and its mouse ortholog p204 are elevated in patients with acute tubular necrosis (ATN) and in renal ischemia/reperfusion (I/R)-induced AKI models.
- Tubule-specific p204 deficiency in mice and IFI16 knockout in HK-2 cells reduce ferroptosis in renal tubular epithelial cells (TECs) under I/R conditions.
- IFI16 binds to PARP-1, enhancing protein PARylation, which activates ATM-p53 signaling, leading to lipid peroxidation and ferrous ion accumulation in TECs.
- IFI16's role in DNA damage response (DDR) depends on its HIN and PYRIN domains.
- Targeting IFI16 may offer a new therapeutic strategy for treating AKI.