Macrophages rescue cells from ferroptotic death.

ABSTRACT: Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation, has a key role in organ injury, degenerative disease, and vulnerability of therapy-resistant cancers. Although substantial progress has been made in understanding the molecular processes relevant to ferroptosis, additional cell-extrinsic processes that determine cell sensitivity toward ferroptosis remain unknown. Here we demonstrate that macrophages co-cultured with ferroptotic cancer cells from various types effectively mitigate cell death induced by GPX4 inhibitors (RSL3 and ML162), GPX4 silencing via shRNA, or the Xc- system inhibitor IKE. Furthermore, macrophages effectively reduced lipid peroxidation in ferroptotic cells. Importantly, macrophage function relies on direct cell-to-cell contact a

SUBMITTER: Hefetz R 

PROVIDER: S-EPMC12827969 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature