LKB1-AMPK axis negatively regulates ferroptosis by inhibiting fatty acid synthesis

Ferroptosis has emerged as a new programmed cell death modality highly relevant to disease. 1 Ferroptosis was initially discovered as an iron-dependent non-apoptotic cell death induced by a serial of ferroptosis-inducing agents (FIN), such as erastin and RSL3. Erastin activates ferroptosis by inhibiting the activity of system Xc − , a cystine-glutamate antiporter, resulting in the depletion of cellular cysteine and glutathione (GSH), thus breaking cellular redox homeostasis. Inactivation of glutathione peroxidase 4 (GPX4), an enzyme required to remove the toxic lipid hydroperoxides can induce ferroptosis without the depletion of cellular cysteine and GSH. 1