| First Author | Xing G | Year | 2022 |
| Journal | EMBO Rep | Volume | 23 |
| Issue | 8 | Pages | e52280 |
| PubMed ID | 35703725 | Mgi Jnum | J:327625 |
| Mgi Id | MGI:7329713 | Doi | 10.15252/embr.202052280 |
| Citation | Xing G, et al. (2022) PPARalpha alleviates iron overload-induced ferroptosis in mouse liver. EMBO Rep 23(8):e52280 |
| abstractText | Ferroptosis is an iron-dependent form of non-apoptotic cell death implicated in liver, brain, kidney, and heart pathology. How ferroptosis is regulated remains poorly understood. Here, we show that PPARalpha suppresses ferroptosis by promoting the expression of glutathione peroxidase 4 (Gpx4) and by inhibiting the expression of the plasma iron carrier TRF. PPARalpha directly induces Gpx4 expression by binding to a PPRE element within intron 3. PPARalpha knockout mice develop more severe iron accumulation and ferroptosis in the liver when fed a high-iron diet than wild-type mice. Ferrous iron (Fe(2+) ) triggers ferroptosis via Fenton reactions and ROS accumulation. We further find that a rhodamine-based "turn-on" fluorescent probe(probe1) is suitable for the in vivo detection of Fe(2+) . Probe1 displays high selectivity towards Fe(2+) , and exhibits a stable response for Fe(2+) with a concentration of 20 muM in tissue. Our data thus show that PPARalpha activation alleviates iron overload-induced ferroptosis in mouse livers through Gpx4 and TRF, suggesting that PPARalpha may be a promising therapeutic target for drug discovery in ferroptosis-related tissue injuries. Moreover, we identified a fluorescent probe that specifically labels ferrous ions and can be used to monitor Fe(2+) in vivo. |
