Table 1.

Mechanisms underlying ferroptosis

Group	Pathways	Key targets	Mechanisms
The exogenous pathway	Inhibition of system Xc- induced ferroptosis	system Xc-, GPX4, p53	system Xc-/GSH/GPX4/ROS/Lipid ROS
			p53/ system Xc-
The endogenous pathway	Lipid metabolism-induced ferroptosis	ACSL4, LPCAT3, LOX	PUFAs/ ACSL4 and LPCAT3/PUFA-PE/LOX/ Lipid ROS
	Iron metabolism-regulated ferroptosis	TRF1, Ferritin, LIP, Fpn, HO-1, HSPB1, NCOA4, NRF2	Fe3+/ TFR1/ STEAP3/ Fe2+/ DMT1 or ZIP8/14/LIP/ROS
			Fe2+/ Fpn/ Fe3+
			HO-1/ Fe2+/LIP
			HSPB1/ TRF1
			NCOA4/ Ferritin/ Fe2+/LIP
			NRF2/ TRF1, Ferritin, HO-1, Fpn/ Fe2+/LIP
	Ferroptosis with mitochondrial involvement	GPX4, DHODH, NRF2, VDACs	ATP/AMPK/acetyl-CoA carboxylase
			TCA cycle/ electron transport and fatty acid biosynthesis
			GPX4/ CoQ/CoQH2
			DHODH/ CoQ/CoQH2
			NRF2/ mitochondrial biogenesis
			NRF2/ mitophagy (P62-dependent, PINK1/Parkin-independent)
			NRF2/ proteasomal genes/ mitochondrial fission
			NRF2/ MFN2/ mitochondrial fusion
			Erastin/VDACs/ Lipid ROS
	Others	FSP1, GPX4, P53	FSP1-COQ10-NAD(P)H
			P53/STAT1/ALOX15/Lipid ROS
			Sulfur transfer pathway

ACSL4 Acyl-CoA synthetase long-chain family member 4; AMPK: AMP-activated protein kinase; DHODH: dihydroorotate dehydrogenase; DMT1: divalent metal transporter 1; GPX4: glutathione peroxidase 4; GSH: glutathione; HO-1: Heme oxygenase-1; HSPB1: heat shock protein B1; LIP: unstable iron pool; LOX: lipoxygenase; LPCAT3: lysophosphatidylcholine acyltransferase 3; MFN2: mitochondrial fusion protein 2; NCOA4: nuclear receptor coactivator 4; NRF2: nuclear factor red lineage 2 related factor 2; PINK1: PTEN-induced kinase 1; PUFAs: polyunsaturated fatty acids; ROS: reactive oxygen species; STEAP3: six-transmembrane epithelial antigen of prostate 3; TFR1: transferrin receptor protein 1; VDACs : mitochondrial voltage-dependent anion channels;ZIP8/14 zinc-iron regulatory protein family 8/14