Table 1.

Main types of PTM in ferroptosis.

PTM category	Substrates	Key regulators	Effects of PTM in ferroptosis	Ref
Ubiquitination	FSP1	TRIM21, TRIM69, TRIM56	K63-linked ubiquitination enhances plasma membrane localization of FSP1 and inhibits ferroptosis; K48-linked ubiquitination enhances degradation of FSP1 and promotes ferroptosis	[56,143,145]
Phosphorylation	DHODH	LOXL3	Enhances degradation of DHODH and promotes ferroptosis	[66]
	TFRC	HUWE1, BTRC	Enhances degradation of TFRC and inhibits ferroptosis	[108,109]
	LTF	NEDD4L	Enhances degradation of LTF and promotes ferroptosis	[110]
	SLC40A1	RNF217, USP35	Enhances degradation of SLC40A1 and promotes ferroptosis	[111,112]
	IRP2	FBXL5	Enhances degradation of IRP2 and inhibits ferroptosis	[114]
	SLC7A11	BTRC, HECTD3, NEDD4L, SOCS2, SYVN1, TRIM26, ZRANB1, OTUB1, USP20	Enhances degradation of SLC7A11 and promotes ferroptosis	[6,[115], [116], [117], [118], [119], [120], [121], [122]]
	GPX4	FBXO31, NEDD4, NEDD4L, STUB1, TRIM21, TRIM25, TRIM26, TRIM59, LUBAC, OTUB1, OTUD5, USP31	Enhances degradation of GPX4 and promotes ferroptosis	[[126], [127], [128], [129], [130], [131], [132], [133], [134]]
	ACSL4	RNF146, NEDD4L, MARCHF6	Enhances degradation of ACSL4 and inhibits ferroptosis	[[146], [147], [148]]
	GSTP1	SMURF2	Enhances degradation of GSTP1 and promotes ferroptosis	[34]
	VDAC2/3	NEDD4, FBXW7	Enhances degradation of VDAC2/3 and inhibits ferroptosis	[150,151]
	NFE2L2	KEAP1, MIB1, USP11	Enhances degradation of NFE2L2 and promotes ferroptosis	[87,154,155] [156]
	HELLS	DCAF8, USP5, USP11	Enhances degradation of HELLS and promotes ferroptosis	[[158], [159], [160]]
	NCOA4	TRIM7, FBXW7	Enhances degradation of NCOA4 and inhibits ferroptosis	[161,162]
	BECN1	USP11	Enhances degradation of BECN1 and inhibits ferroptosis	[163]
	GPX4	CKB	Decreases degradation of GPX4 and inhibits ferroptosis	[58]
Acetylation	ACSL4	PKCBII	Enhances dimerization of ACSL4 and promotes ferroptosis	[63]
	HSPB1	PKC	Enhances function of HSPB1 and inhibits ferroptosis	[64]
	EIF4E	NA	Enhances formation of EIF4E-ALDH1B1 complex and promotes ferroptosis	[33]
	UMPS	AMPK	Enhances function of DHODH and inhibits ferroptosis	[65]
	HPCAL1	PRKCQ	Enhances function of HPCAL1 and promotes ferroptosis	[70]
	BECN1	AMPK	Enhances function of BECN1 and promotes ferroptosis	[71]
	TP53	CREBBP, SIRT1	Enhances function of TP53 and promotes ferroptosis	[76,77]
O-GlcNAcylation	ALOX12	CTH	Enhances function of ALOX12 and promotes ferroptosis	[78]
	HSPA5	EP300	Enhances function of HSPA5 and inhibits ferroptosis	[79]
	Histone	KAT5, EHMT2, SIRT1	Context-specific effects	[81,83]
	SLC7A11	OGT	Enhances function of SLC7A11 and inhibits ferroptosis	[84]
SUMOylation	YAP1	OGT	Enhances function of YAP1 and promotes ferroptosis	[85,86]
	ZEB1	OGT	Enhances function of ZEB1 and promotes ferroptosis	[85,86]
	JUN	OGT	Enhances function of JUN and promotes ferroptosis	[89]
	Ferritin	OGT	Enhances binding of ferritin and NCOA4 and promotes ferroptosis	[90]
	ACSL4	SENP1	Decreases degradation of ACSL4 and promotes ferroptosis	[92]
Methylation	HIF1A	SENP1	Enhances function of HIF1A and promotes ferroptosis	[93]
	ACSL4	CARM1	Enhances degradation of ACSL4 and inhibits ferroptosis	[97]
N-myristoylation	NFE2L2	CARM1	Decreases function of NEF2L2 and promotes ferroptosis	[98]
	OTUB1	SETD7	Decrease binding of OTUB1 and UBE2N, and promotes ferroptosis	[99]
	FSP1	ACSL1	Enhances plasma membrane localization of FSP1 and inhibits ferroptosis	[43]
Palmitoylation	SLC7A11	ZDHHC8	Decreases degradation of SLC7A11 and inhibits ferroptosis	[102]
Oxidative modification	PRDX3	NA	Enhances function of PRDX3 and promotes ferroptosis	[104]