Fig. 1: Drivers of ferroptosis.

The initiators of ferroptosis include lipid metabolism and iron metabolism. In lipid metabolism, adrenoic acid and arachidonic acid in a series of enzymatic reactions culminate in the production of PUFA to promote ferroptosis. In iron metabolism, the binding of transferrin (TF) and transferrin receptor (TFRC) on the membrane drives extracellular Fe³⁺ into the cytosol, followed by the reduction of Fe³⁺ to Fe²⁺ by STEAP3, which is transported between different organelles under the action of SLC39A14, DMT1, and TRPML1/2, and finally sinks into the Lip. Also, various organelles are extensively involved in ferroptosis; the tricarboxylic acid cycle in mitochondria generates enormous amounts of ROS, and metabolic activity or oxidative stress in the Golgi, endoplasmic reticulum, and lysosomes can trigger ferroptosis.