A fin-like structural loop in GPX4 is critical for anchoring the enzyme to cellular membranes, thereby preventing ferroptosis. A patient-associated R152H mutation destabilizes this loop, leading to fe...

Tumor reliance on antioxidant defenses creates a vulnerability to ferroptosis, yet strategies to therapeutically disable these systems remain limit...

D’Ambrosio et al. screen 10,480 electrophilic compounds for senolytic effects and show that senolytic chloroacetamides or GPX4 inhibitors selectively kill senescent cells by ferroptosis.

Scientific Reports - TNF-α inhibits Epstein Barr virus reactivation through the GPX4 mediated glutathione pathway

Fan et al. report a role for PRMT5 in regulating GPX4 stability and ferroptosis sensitivity through arginine methylation, which may be targeted to inhibit tumour development.

Interferon-γ (IFNγ)-activated calcium/calmodulin-dependent protein kinase II (CAMK2) phosphorylates phosphoserine aminotransferase 1 (PSAT1) at serine 337 (S337), enabling glutathione peroxidase 4 (GP...

Selenocysteine, incorporated into polypeptides at recoded termination codons, plays an essential role in redox biology. Using GPX1 and GPX4, selenoenzymes that mitigate oxidative stress, as reporters,...

Membrane protection against oxidative insults is achieved by the concerted action of glutathione peroxidase 4 (GPX4) and endogenous lipophilic antioxidants such as ubiquinone and vitamin E. Deficienci...

D’Ambrosio et al. screen 10,480 electrophilic compounds for senolytic effects and show that senolytic chloroacetamides or GPX4 inhibitors selectively kill senescent cells by ferroptosis.

Zheng and Zhang et al. identify N-acetyl-l-cysteine (NAC) and its enantiomer N-acetyl-d-cysteine (d-NAC) as direct reducing substrates of glutathione peroxidase 4 (GPX4). They further reveal a broad range of reducing substrates for GPX4 in vitro. This study suggests GPX4 may utilize other reducing substrates to counteract ferroptosis upon glutathione deficiency.

Liu et al. identify the hypoxia-induced lncRNA SHIELD that protects cancer cells from ferroptosis by enhancing the translation of a key antioxidant enzyme. The study links hypoxic adaptation to ferroptosis resistance and suggests a potential therapeutic strategy to overcome sorafenib resistance in liver cancer.

Learn how senolytic drugs target zombie cells and SASP to fight aging. From fisetin to DNA aptamers, explore the science of longevity medicine in 2026.

Ferroptosis, a regulated form of cell death, is determined by iron-dependent lipid peroxidation. A selenoenzyme called glutathione peroxidase 4 (GPX4) detoxifies phospholipid hydroperoxides at the heart of this process. As the pivotal gatekeeper of ferroptosis, GPX4 is implicated in a wide range of pathologies, including cancer, neurodegeneration, acute renal failure, and infection. In this review, we discuss how GPX4 transcription and mRNA stability are controlled by transcription factors, epigenetic modifications, and noncoding RNAs and how GPX4 degradation and activity are modulated by post-translational modifications, including ubiquitination, phosphorylation, palmitoylation, methylation, hydroxylation, and lactylation. We also summarize new therapeutic methods targeting GPX4, namely the ferroptosis inducers for cancer therapy and ferroptosis inhibitors that prevent ferroptosis-related damage.

Red blood cell (RBC) membrane lipid peroxidation during blood bank storage profoundly impacts transfusion efficacy; however, the genetic determinants …