bioRxivJClub
A GPX4 phosphorylation switch by FGFR1 guards against ferroptosis
bioRxiv · · Preprint · Open access
Song, Wang + 15 more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
FGFR1 phosphorylates GPX4 at Tyr180/Tyr196 to enhance GPX4 activity and suppress ferroptosis, and this switch is essential in a phosphorylation-deficient GPX4 knock-in mouse.
- Why it matters: Cells need rapid ways to tune ferroptosis sensitivity to extracellular signals, but the direct molecular control linking receptor signaling to GPX4 activity was unclear.
- What they did: FGFR1 directly binds and, in a kinase-dependent manner, phosphorylates GPX4 at Tyr180/Tyr196 using FGFR1 Tyr730 as a docking site; in cardiac ischemia/reperfusion, FGF-1DeltaNT reactivates the axis.
- The result: The FGFR1-GPX4 axis is suppressed during ischemia/reperfusion, and FGF-1DeltaNT protects against ferroptosis-mediated damage, whereas phosphorylation-deficient GPX4 knock-in mice are hypersensitive and non-responsive to the agonist.
The findingWhy it mattersWhat they didThe result
- Open access