Table 11.

Epigenetic and posttranslational modification of ferroptosis in lung diseases

Disease	Modification	Targets	Biological functions	Ref
Acute lung injury	Acetylation	p53/SLC7A11	STAT6 alleviates acute lung injury through inhibiting ferroptosis via competitively binding with CREB-binding protein (a critical acetyltransferase of p53 acetylation), which inhibits p53 acetylation and transcriptionally restores SLC7A11 expression.	471
Acute lung injury	Acetylation	p53/SLC7A11/GPX4	Decreased SIRT1 trigger heat stress-induced lung epithelial cells injury through inducing ferroptosis via increasing acetylation of p53, which transcriptionally inhibits SLC7A11.	472
Acute lung injury	Phosphorylation	PERK	mtROS-initiated endoplasmic reticulum membrane (MAMs) dysfunction is partially implicated in arsenic-evoked ferroptosis and ALI.	469
Acute lung injury	Phosphorylation	STAT3	Nrf2 works together with and promotes phosphorylation of STAT3, through which collaborate to upregulate SLC7A11 to inhibit ferroptosis in intestinal ischemia/reperfusion-induced acute lung injury (IIR-ALI) model.	470
Sepsis-Induced Acute Lung Injury	m6A	GPX4	NETs induce ferroptosis through METTL3-induced m6A modification of GPX4 in the pathogenesis of sepsis-associated ALI.	473
Sepsis-Induced Acute Lung Injury	ncRNA	Nrf2/GPX4	miR-125b-5p in adipose derived stem cells exosomes alleviates the inflammation induced PMVECs ferroptosis in sepsis induced acute lung injury via regulating Keap1/Nrf2/GPX4 expression, hence improve the acute lung injury in sepsis.	480
Sepsis-Induced Acute Lung Injury	Phosphorylation	GSK3β/Nrf2/GPX4	Inhibition of MUC1 aggravates lung injury through triggering ferroptosis via increasing the expression level of Keap1, reducing the phosphorylation level of GSK3β, inhibiting the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4.	474
Sepsis-Induced Acute Lung Injury	Ubiquitination	AUF1/Nrf2/ATF3	FBXW7 mediates protein degradation of AUF1.AUF1 alleviate sepsis-induced acute lung injury through inhibiting ferroptosis by upregulating Nrf2 and down-regulating ATF3.	475
COPD	Methylation	RAP1A	NF-κB/RelA-mediated PRMT7 upregulaioned expression induces mono-methylation of histones at enhancers can regulate Rap1a expression, which is crucial for MAPK signaling downstream of G-protein coupled activation, integrin activation, and the subsequent adhesion and migration ability of monocytes Further, inflammatory macrophages via ALOX5-mediated release of LTB4 induced increased expression of ACSL4 in AT2 cells increasing susceptibility to cigarette smoke-induced ferroptosis and tissue injury.	481
COPD	Methylation	Nrf2/GPX4	Hypermethylation of the Nrf2 promoter-induced inhibition of Nrf2 induces ferroptosis through inhibiting GPX4 in cigarette smoke extract treated human bronchial epithelial (HBE) cells.	482
COPD	Ubiquitination	MFG-E8	Cigarette smoke-induced diminished USP14 expression leads to the proteasomal degradation of MFG-E8, which aggravates bronchial epithelial cell ferroptosis.	483
Pulmonary fibrosis	Methylation	GPX4 and FSP1	Upregulation de novo methylation regulator UHRF1 sensitively elevates CpG site methylation levels in promoters of both GPX4 and FSP1 genes and induces the epigenetic repression of both genes, subsequently leading to ferroptosis in chemically interfered AEC2 cells.	630
Pulmonary epithelial senescence	Acetylation	USP3/SIRT3/p53/SLC7A11	PM2.5 triggers pulmonary epithelial senescence and ferroptosis through decreasing USP3, by which leads to SIRT3 degradation via ubiquition proteasome pathway, thereby increasing p53 acetylation, which transcriptionally activates p21 and inhibits SLC7A11.	598

AUF1 U-richelement(ARE)-binding factor1, COPD chronicobstructive pulmonary disease, Ptgs2 prostaglandin-endoperoxide synthase 2, LOXs lipoxygenases, TfR1 transferrin receptor 1, NETs neutrophil extracellular traps, IRI ischemia/reperfusion injury, TMEM16A transmembrane member 16A, STAT3 signal transducer and activator of transcription 3