Ferroptosis execution: Is it all about ACSL4?

ACSL4 is generally considered to be universally required for ferroptosis, a form of cell death induced by phospholipid peroxidation. In this issue of Cell Chemical Biology, Magtanong et al. (2022) report the surprising finding that ACSL4 is only required for ferroptosis in certain circumstances, raising interesting questions about the regulation of this cell death pathway. ACSL4 is generally considered to be universally required for ferroptosis, a form of cell death induced by phospholipid peroxidation. In this issue of Cell Chemical Biology, Magtanong et al. (2022) report the surprising finding that ACSL4 is only required for ferroptosis in certain circumstances, raising interesting questions about the regulation of this cell death pathway. Context-dependent regulation of ferroptosis sensitivityMagtanong et al.Cell Chemical BiologyJuly 8, 2022In BriefThe genetic regulation of ferroptosis remains poorly understood. Magtanong et al. demonstrate that ACSL4, AGPS, and other lipid metabolic genes are context-dependent ferroptosis regulators that are not universally essential for this process. Results suggest that there may not exist a single ferroptosis genetic regulatory mechanism in all cells and conditions. Full-Text PDF