GPX4 (Glutathione Peroxidase 4)

While canonical ferroptosis is usually triggered by inducers, such as erastin and RSL-3, or by glutathione peroxidase (GPX)4 loss, how ferroptosis occurs naturally in vivo without these triggers has been unclear...OSBPL8 and GPX1 are overexpressed in cancers; knockdown of either promotes ROS-induced ferroptosis and suppresses tumor growth. Our data link the GPX1-OSBPL8 axis to in vivo ferroptosis and tumor suppression.

CD8+ cytotoxic T lymphocytes and CD4+ helper T lymphocytes were promoted by HZ-1 both in spleens and tumors. To sum up, the interaction of HZ analogs with multiple G4s formulates a new concept for anticancer strategies.

Transgenic mouse models are reported where they help define a biological concept. We deliberately did not strive to cover in this work all the biochemical mechanisms of selenoenzymes or their interactions with effector proteins.

These findings demonstrate that acquired sorafenib resistance in HCC is associated with a stable NRF2-driven transcriptional and metabolic reprogramming that enhances antioxidant capacity, suppresses ferroptosis and promotes tumor cell survival. Targeting NRF2-regulated redox metabolism may therefore represent a promising strategy to overcome therapeutic resistance in HCC.

HMB protects lungs in experimental sepsis by inhibiting NF-κB inflammation, reducing ER and mitochondrial apoptosis, and boosting antioxidant defenses via NRF2/GPX4. These findings support its potential as adjunct therapy for sepsis-induced ALI.

We find that induction of single-cell ferroptosis involves heterogeneous death profiles, with necrosis and apoptosis occurring in parallel within cell populations. These findings identify factors that control propagation and underscore lysosomes as critical to the execution of ferroptosis.

Mechanistically, SREBP1 silencing promotes ubiquitination-mediated degradation of the Nrf2 protein, thereby suppressing the expression of XCT and GPX4, ultimately triggering ferroptosis in ovarian cancer cells. Our findings establish SREBP1 as a key mediator of ferroptosis resistance and nominates it as both a therapeutic target and a potential prognostic biomarker in ovarian cancer.Schematic diagram illustrating the mechanism whereby silent SREBP1 mediates the Nrf2/XCT/GPX4 pathway to induce ferroptosis in ovarian cancer cells.

Molecular docking validated high-affinity binding between betaine and Nrf2. Collectively, betaine could exert neuroprotective effects by alleviating ferroptosis via activation of the Nrf2 pathway, thereby positioning it as a potential candidate for targeting ferroptosis-driven neurodegeneration in AD.

Beclin1 knockdown and DHODH overexpression can reduce DOX-induced liver injury by preventing ferroptosis and autophagy.

In vivo, xenograft models further validated that BUB1 silencing significantly reduces tumor volume, accompanied by modulation of ferroptosis-related genes in tumor tissues. Collectively, our findings identify BUB1 as a novel prognostic biomarker and therapeutic target for LUAD, revealing a new regulatory mechanism by which BUB1 promotes LUAD progression through the activation of the STAT3/GPX4 axis to suppress ferroptosis.

This programmed lysis releases a synergistic cocktail of bacterial PAMPs and tumor-derived DAMPs, which effectively remodels the immunosuppressive TME and initiates a potent systemic antitumor immune response. By integrating metabolic reprogramming, sensitized ferroptosis, and on-demand immune activation through simple surface engineering, this study provides a highly translatable and safe paradigm for the next generation of living bacterial therapeutics.

Small molecule inhibitors such as RSL3 and ML210 trigger ferroptosis by targeting glutathione peroxidase 4 (GPX4), a key enzyme that neutralizes lipid peroxides. Tumors derived from GPX4i-resistant cells compared to parental cells had unique metabolic and lipidomic profiles, were associated with a shift toward an epithelial-like state (decreased vimentin, increased EpCAM expression), formed decreased spontaneous metastases from primary tumors, but had no differences in overall metastatic burden upon intravenous injection. Collectively, these data demonstrate that long-term maintenance with GPX4-inhibitors in vitro leads to altered metastatic profiles in vivo.