Apoptosis and Ferroptosis Research

4HB mRNA and Death-Pathway Attribution

2026-11-06

Compared with full-length MLKL mRNA, MLKL four-helix-bundle (4HB) mRNA produced stronger lytic death and immunogenic-cell-death signals, including greater cytotoxicity in RIPK3-deficient A549 and CT26 cells and in B16 cells. Inhibitor experiments support a caspase-independent, necroptosis-like interpretation, but the study does not establish ferroptosis. Compared with ALC-0315 LNPs, tumour-customized delivery improved tumour selectivity and immune recruitment in model-specific settings; it reduced toxicity in 4T1 tumours but did not eliminate liver toxicity in B16 tumours.

SENP1–SIRT3–IDH2 and Ferroptosis Resistance

2026-11-04

Chen and colleagues report that, compared with vector-control MCF-7 and MDA-MB-231 breast cancer cells, IDH2 overexpression preserved glutathione and GPX4, reduced lipid-peroxidation readouts, and weakened the viability loss associated with erastin; IDH2 knockdown produced the opposite pattern. In xenografts, erastin reduced growth in control tumors but not in IDH2-overexpressing tumors. Mechanistically, the IDH2 K413R deacetylation mimic rescued the reductions in NADPH, glutathione, and viability caused by SIRT3 knockdown, linking SIRT3-dependent IDH2 deacetylation to ferroptosis resistance.

Mitochondrial Apoptosis in HCC Nanomedicine

2026-11-02

AMPK, Energy Stress and Neuronal Ferroptosis

2026-10-30

Yong et al. report that energy-stress interventions reduced cell death, oxidative stress and lipid-peroxidation readouts in APP-, α-synuclein A53T- and polyQ74-expressing SH-SY5Y cells; GPX4 restoration and ACSL4 reduction were specifically reported in the APP-overexpressing analysis. In the Aβ-expressing Caenorhabditis elegans model, aak-2 knockdown weakened 2-deoxy-D-glucose-associated behavioral and oxidative protection. In 3xTg-AD mice, 2-deoxy-D-glucose and liproxstatin-1 each improved spatial-memory measures compared with untreated 3xTg-AD mice and reduced hippocampal ferroptosis-associated markers. The results support AMPK–ACC1 signaling as a contributor to ferroptosis suppression, but do not establish that ferroptosis is the exclusive death pathway or prove AMPK necessity in mammalian neurons.

GPRC6A–Duox1 Links Testosterone to Cell Death

2026-10-28

Compared with control-siRNA human outer-root-sheath cells, GPRC6A or Duox1 knockdown reduced testosterone-associated TUNEL signal. In primary mouse keratinocytes, GPRC6A- or Duox1-deficient cells showed less TUNEL signal than wild-type cells, and in testosterone-challenged mice, knockout follicles resisted shortening relative to wild type. The study supports a GPRC6A–Ca2+–Duox1–H2O2-associated cell-death pathway, but it does not establish caspase-dependent apoptosis or ferroptosis.

Does Leptin Loss Prove Liver Cell Death?

2026-10-14

In female lepa−/− medaka, hepatic steatosis and altered stress- and apoptosis-associated gene expression were compared with wild-type females. The study supports a stress-associated transcriptional state, not confirmed apoptosis, and provides no evidence sufficient to attribute the phenotype to ferroptosis.

IRE, CAR-NK Killing, and Ferroptosis

2026-10-09

In this preclinical HCC study, IRE or PEF sensitized Huh-7, Hepa1c1c7, and patient-derived tumor models to NK-cell killing. Compared with PEF-treated targets paired with control NK cells or untreated targets paired with CAR-NK cells, the combined treatment increased caspase-3/7-associated death; compared with IRE alone or IRE plus control NK cells, IRE plus GPC3 CAR-NK cells produced stronger tumor suppression in mice. NAC rescue linked sensitization to ROS, but the study did not establish caspase dependence or provide ferroptosis-specific evidence.

TREM-1–NLRP3 Pyroptosis in Septic AKI

2026-10-07

In a 24-hour mouse sepsis-associated acute kidney injury model, Trem1-deficient septic mice had less tubular injury, renal dysfunction, inflammation, and NLRP3–caspase-1–GSDMD signaling than wild-type septic mice. NLRP3 inhibition reduced injury in wild-type septic mice, whereas NLRP3 activation worsened injury in Trem1-deficient septic mice, supporting TREM-1 as an upstream amplifier of pyroptotic signaling. Apoptosis-associated markers changed in parallel but were not causally tested, and the study provides no evidence for ferroptosis.

How TUT1 Loss Drives Neural Stem-Cell Death

2026-10-05

Compared with control neural stem cells, Tut1 loss weakened U6 snRNA association with Lsm4 and Lsm8, disrupted RNA splicing, and increased DNA-damage and cleaved caspase-3 signals. Relative to Tut1 loss alone, simultaneous Trp53 deletion restored pallial structures and prevented cell death, while U6 snRNA carrying six 3′ uridines rescued survival more strongly than versions carrying zero or two uridines. By contrast, Usb1-null embryonic stem cells retained proliferation and pluripotency relative to wild-type cells. The study therefore supports p53-dependent, caspase-3-associated cell death downstream of spliceosomal failure, but does not establish ferroptosis or fully prove caspase dependence.

dsRNA Impurities: Pyroptosis, Not Ferroptosis

2026-10-02

Liu et al.’s 2026 review identifies a supported dsRNA-associated death pathway—NLRP1, caspase-1, and GSDMD-mediated pyroptosis—but reports no direct apoptosis or ferroptosis experiments. Compared with silica-based purification of self-amplifying mRNA, cellulose purification is summarized as producing lower dsRNA and higher protein expression. Because tangential-flow filtration can remove small molecules and some protein while leaving similarly sized dsRNA, purification controls are essential before assigning cell-growth inhibition or death to an mRNA mechanism.

Does CEBPA–ALOX15B Drive Osteoblast Ferroptosis?

2026-09-30

Wang et al. examined whether the CEBPA–ALOX15B axis links osteoblast ferroptosis to postmenopausal osteoporosis. In hFOB 1.19 cells, ALOX15B knockdown compared with sh-NC, and compared with Erastin-treated cells, reduced Fe2+, MDA, ROS, and PTGS2 while increasing GSH-related defenses and GPX4. CEBPA knockdown effects were partially reversed by ALOX15B overexpression. In ALOX15B-knockout ovariectomized mice versus wild-type ovariectomized mice, BMD, BV/TV, and trabecular thickness increased while trabecular separation decreased, although values remained below knockout-sham levels. The results support a pathway-level ferroptosis model, but Annexin V/PI and TUNEL do not establish apoptosis, and the study did not test caspase dependence or a ferroptosis-selective rescue.

tRNA m1A58, Nrf1 and HSPC Apoptosis

2026-09-28

In zebrafish embryos, the study links TRMT61A/TRMT6-dependent tRNA m1A58 modification to Nrf1 translation and HSPC production. TUNEL and p53-knockdown rescue support p53-dependent apoptosis; the reported experiments do not establish ferroptosis or caspase dependence.

H-151 Blocks Ferroptosis Through Radical Trapping

2026-09-25

Yin et al. report that H-151 protects cells from ferroptosis independently of STING by limiting radical-driven lipid peroxidation. Cell experiments, biochemical radical-trapping assays and a prophylactically treated mouse renal ischemia–reperfusion model support this dual activity. The study does not establish an apoptosis mechanism or test caspase dependence.

Q-VD(OMe)-OPh in Apoptosis Assay Workflows

2026-09-23

Use Q-VD(OMe)-OPh to test whether caspase-dependent apoptosis contributes to a treatment response—not to assume every loss of viability is apoptotic. This workflow connects the inhibitor’s broad caspase coverage with practical controls for colorectal cancer studies, while distinguishing apoptosis from the autophagy and ferroptosis also reported in cetuximab-resistant cells.

AZD0156: Precision ATM Kinase Inhibitor Workflows

2026-09-22

AZD0156 enables controlled interrogation of ATM-dependent DNA repair, checkpoint signaling, and metabolic adaptation in cancer models. This workflow-focused guide translates evidence on macropinocytosis and branched-chain amino acid uptake into practical assay designs, controls, and troubleshooting strategies.