Table 4 Acetylation modifications regulating ferroptosis.

From: Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation

Gene/Protein name

Acetylation modification sites

Acetylation regulatory mechanisms

Biological function (with reference numbers)

p53

K382, K120, K117, K161, K162, K98, K136

p53 3KR/3KR (K117,161,162 mutations) activates ferroptosis; adding K98 mutation eliminates pro-ferroptotic effect; adding K136 mutation abolishes tumor suppression.

Acetylation state downregulates SLC7A11 expression, thereby promoting ferroptosis [212,213,214,215,216,217,218].

PRMT1

K145

LPCAT2 increases the acetylation of PRMT1 at the K145 site

A hyperacetylated state leads to the loss of PRMT1-mediated asymmetric dimethylation of histone H4 arginine 3 at the LC7A11 locus, constraining LC7A11 transcriptional activation and promoting ferroptosis [220].

STAT3

Sites not specified

Acetylation enhances transcriptional activity.

Acetylated STAT3 binds to consensus DNA response elements in promoters of GPX4, SLC7A11, and FTH1, inhibiting ferroptosis [231].

HOXB9

K27

The interaction between HOXB9 and the acetyltransferase p300/CBP-associated factor enhances the K27 acetylation level of HOXB9.

Acetylation of HOXB9 promotes its degradation, weakening HOXB9’s ability as a transcription factor to regulate SLC7A11 expression [219].

FSP1

K168

SLC25A1/ACLY/KAT2B pathway maintains acetylation, preventing ubiquitination degradation. HDAC3 reverses this.

Acetylation stabilizes FSP1 protein, enhancing its reduction of CoQ10 and vitamin K, inhibiting ferroptosis [235].

DHODH

Sites not specified

Decreased SIRT3 leads to increased acetylation levels.

High acetylation hinders pyrimidine biosynthesis and CoQH2 generation, promoting ferroptosis [236].

GPX4

Sites not specified

Decreased SIRT3 results in hyperacetylation and reduced protein levels.

Hyperacetylation decreases GPX4 protein levels, promoting ferroptosis [234].

HSPA5

K353

EP300 catalyzes acetylation, promoting ferroptosis; HDAC6 limits acetylation.

Acetylation impairs HSPA5’s ability to stabilize GPX4 protein, promoting ferroptosis [233].

TUBORF

K10, K16

ESCO1 associates with TUBORF, catalyzing acetylation of TUBORF at K10 and K16.

TUBORF suppresses the upregulation of SLC7A11 and GPX4 protein expression, enhancing resistance to ferroptosis [232].

ALOX12

Sites not specified

NaHS (hydrogen sulfide donor) alleviates its acetylation.

Acetylation promotes its function in lipid peroxidation. Reducing acetylation protects membrane lipids, inhibiting ferroptosis [239].

SDHA

Sites not specified

TIGAR enhances SIRT5 interaction and reduces SIRT3 interaction, leading to acetylation.

Acetylation inhibits SDH enzyme activity, reducing ROS production and inhibiting ferroptosis [238].

NNT

K1042

IL-1β induces acetylation of NNT at the K1042 site.

NNT K1042 acetylation preserves iron-sulfur clusters, which suppress TFRC expression and promote FTH1 transcription, thereby maintaining iron homeostasis and inhibiting ferroptosis [229].

SLC7A11 (gene)

H3K27 at promoter

H3K27ac serves as a mark recruiting GAS41, activating expression.

Histone H3K27 acetylation promotes SLC7A11 transcription, inhibiting ferroptosis [221].

TUBORF (gene)

H3K27

p300-mediated acetylation of histone H3 lysine 27

TUBORF suppresses the upregulation of SLC7A11 and GPX4 protein expression, enhancing resistance to ferroptosis [232].

GPX4 (gene)

Promoter region

HMGA2 binds the promoter, enhancing enhancer activity via increased H3K4 methylation and H3K27 acetylation.

Histone modifications (including H3K27ac) at the promoter promote GPX4 transcription, inhibiting ferroptosis [225].

FTH1 (gene)

Promoter region

Sirt1 reduces FOXO1 acetylation, weakening DNA binding, thus suppressing FOXO1-mediated inhibition of FTH1 transcription (indirect promotion).

Low FOXO1 acetylation upregulates FTH1 transcription, inhibiting ferroptosis [228].

DPP4 (gene)

H3K9

HMGCL regulates H3K9 acetylation via β-OHB

DPP4 regulates ferroptosis by modulating SLC7A11 protein levels [223].

FSP1 (mRNA)

Cytidine 132 site (ac4C modification)

NAT10 mediates ac4C modification, stabilizing the mRNA transcript.

mRNA ac4C acetylation enhances FSP1 mRNA stability, inhibiting ferroptosis [226].

SLC7A11 (mRNA)

Sites not specified

NAT10 stabilizes mRNA transcript via ac4C modification.

mRNA ac4C acetylation enhances SLC7A11 mRNA stability, inhibiting ferroptosis [222].

  1. p53 tumor protein p53, PRMT1 protein arginine methyltransferase 1, STAT3 signal transducer and activator of transcription 3, HOXB9 homeobox B9, FSP1 ferroptosis suppressor protein 1, DHODH dihydroorotate dehydrogenase, GPX4 glutathione peroxidase 4, HSPA5 heat shock protein family A (Hsp70) member 5, TUBORF tubulin oligomerization and folding regulator, ALOX12 arachidonate 12-lipoxygenase, SDHA succinate dehydrogenase complex flavoprotein subunit A, NNT nicotinamide nucleotide transhydrogenase, SLC7A11 solute carrier family 7 member 11, FTH1 ferritin heavy chain 1, DPP4 dipeptidyl peptidase-4, NAT10 N-acetyltransferase 10, EP300 E1A-binding protein P300, HDAC3 histone deacetylase 3, SIRT3 sirtuin 3, ESCO1 establishment of sister chromatid cohesion N-acetyltransferase 1, TIGAR TP53 induced glycolysis regulatory phosphatase, SIRT5 sirtuin 5, GAS41 glioma-amplified sequence 41, HMGA2 high mobility group AT-hook 2, FOXO1 forkhead box O1, HMGCL 3-hydroxy-3-methylglutaryl-CoA lyase, β-OHB beta-hydroxybutyrate.
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