Longevity & AgingGPX4 controls ferroptosis, and new drugs aim to switch it on or off
Ferroptosis is a form of regulated cell death driven by iron-dependent lipid peroxidation. The selenoenzyme GPX4 acts as its main gatekeeper by detoxifying phospholipid hydroperoxides. This review describes how cells control GPX4 at several levels. Transcription factors, epigenetic modifications, and noncoding RNAs affect GPX4 gene expression and mRNA stability. Post-translational modifications, including ubiquitination, phosphorylation, palmitoylation, methylation, hydroxylation, and lactylation, influence how quickly GPX4 is degraded and how active it is. The review links GPX4 to cancer, neurodegeneration, acute kidney failure, and infection. It also summarizes emerging therapies: ferroptosis inducers that could kill cancer cells, and ferroptosis inhibitors that could protect tissues from damage. Only the abstract was available, so details of specific compounds and the strength of supporting evidence are not covered here.
