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

Dear Editor,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.