Necroptosis in Gpx4^Δ mice is triggered independently of TNFR or CD95 engagement and PARP activation. Lipid peroxidation (A) and ROS accumulation (B) in peripheral blood erythroid cells (TER119⁺) are not significantly affected upon Rip3 deletion. Data are mean ± SE; n ≥ 4; *P < .05, **P < .01, ***P < .001 by ANOVA/Bonferroni. The number of peripheral CD71⁺/TER119⁺ cells remains unaffected (C), and there is no change in red blood cell counts (D), hemoglobin levels (E), hematocrit (F), and reticulocyte counts (G) in Gpx4^Δ mice when treated with etanercept (5 mg/kg) or anti-CD95L neutralizing antibody (50 μg) for 2 weeks. Data are mean ± SE; n ≥ 5. Immunohistochemistry of phospho-H2Ax (pH2Ax) and nuclear counterstain hematoxylin in the spleen (H-I) and the quantification of phospho-H2Ax⁺ foci (J). Image acquisition was performed using a Zeiss Axio Imager M2 with a 20×/0.5 EC Plan Neofluar objective (magnification ×200). Data are mean ± SE; n ≥ 3; ***P < .001 by Student t test. The number of peripheral CD71⁺/TER119⁺ cells remains unaffected (K), and there is no change in red blood cell counts (L), hemoglobin levels (M), hematocrit (N), and reticulocyte counts (O) in Gpx4^Δ mice when treated with the PARP inhibitor olaparib (5 mg/kg) for 2 weeks. Data are mean ± SE; n ≥ 5. DMSO, dimethylsulfoxide; PBS, phosphate-buffered saline.