Table 5 Acetylation modifications regulating pyroptosis.
From: Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation
Gene/Protein name | Acetylation modification sites | Acetylation regulatory mechanisms | Biological function (with reference numbers) |
|---|---|---|---|
NLRP3 (gene) | H3 (K9, K14, K27), H4 | P300 increases H3K9 and H3K14 acetylation at the promoter; STAT3-EP300 promotes histone H3 and H4 acetylation; Lactate can promote histone H3K9 acetylation. | Histone hyperacetylation (H3K9ac, H3K14ac, H3K27ac, H4ac) at the promoter promotes NLRP3 gene transcription, foundational for pyroptosis [254, 258,259,260]. |
p65 | Sites not specified | Its acetylation can inhibit NLRP3 expression; HDAC6 reduces its acetylation. | p65 acetylation inhibits pyroptosis; deacetylation promotes pyroptosis [250]. |
GSDMD | K248 | HDAC4 mediates deacetylation; PP1 inactivates HDAC4, promoting acetylation. | Acetylation enhances GSDMD pore-forming function, promoting pyroptosis execution [286]. |
NLRC4 | K71, K272 | SIRT3 mediates deacetylation. | Deacetylation promotes its activation, thereby promoting pyroptosis [268]. |
Parkin | Sites not specified | Exogenous Zn²⁺ inhibits SIRT1 activity, upregulating its acetylation. | Acetylation promotes Parkin-mediated mitophagy (mitochondrial clearance), thereby inhibiting NLRP3 inflammasome activation and pyroptosis [273]. |
HSP90 | Sites not specified | HDAC6 causes deacetylation. | Deacetylation enhances HSP90 binding to NLRP3 protein, preventing NLRP3 degradation, thereby promoting pyroptosis [43, 274, 275]. |
ULK1 | K68 | Increased HDAC2 leads to its deacetylation. | Deacetylation weakens ULK1-mediated autophagy (a cellular clearance mechanism), inhibiting NLRP3 degradation, thus driving pyroptosis [279]. |
α-tubulin | K40 | SIRT2 agonists resveratrol (5 μM) and NAD+ (10 μM) reduce K40 acetylation from >60% to ~20%. | Acetylated α-tubulin promotes dynein-mediated transport of mitochondria (carrying ASC) to the perinuclear area, enhancing ASC proximity to NLRP3 on the ER, promoting pyroptosis [283, 284]. Deacetylation inhibits pyroptosis. |
GSDMD(gene) | H3K27 | BRD4 upregulates H3K27 acetylation at the GSDMD gene promoter region | Increased GSDMD expression promotes pyroptosis [261]. |
SMAD7 (gene) | H3K27 | HDAC2 catalyzes the deacetylation of H3K27 at the SMAD7 promoter. | Deacetylation of SMAD7 suppresses its expression, thereby inhibiting TGF-β–mediated activation of NF-κB and exerting an anti-pyroptotic effect [245]. |
ERG (gene) | Sites not specified | HDAC11 may regulate the acetylation level of ERG | Low acetylation levels of ERG activate NF-κB and promote pyroptosis [248]. |
ULK1 (mRNA) | Sites not specified | Reduced NAT10 expression leads to decreased ac4C modification of ULK1 mRNA. | Loss of ULK1 enhances activation of the STING-IRF3 signaling pathway, thereby leading to increased pro-pyroptotic NLRP3 inflammasome in neutrophils [257]. |
ATG5 (gene) | H3K27 | Increased HDAC3 expression reduces H3K27 acetylation at ATG5. | The HDAC3 inhibitor BRD3308 upregulates ATG5 expression by suppressing deacetylation, which in turn reduces the accumulation of reactive oxygen species and inhibits pyroptosis [263]. |
VDAC (gene) | H3K27 | BRD4 Regulates H3K27 Acetylation at the VDAC Gene Promoter Region | Upregulation of VDAC and recruitment of NLRP3 promote the occurrence of pyroptosis [261]. |
SOD2 (gene) | H3K27 | Nrf2 can recruit EP300, thereby mediating H3K27 acetylation of SOD2 | SOD 2 in a hyperacetylated state resists oxidative stress and suppresses pyroptosis [266]. |
PLK1 (gene) | H3K27 | Elevated BRD4 levels recognize P300-dependent H3K27 acetylation and promote the expression of the PLK1 gene promoter | PLK1 induces activation of the NLRP3 inflammasome and subsequent pyroptosis [270]. |
