Research progress in ferroptosis regulation in the treatment of liver diseases

doi:10.3969/j.issn.1674-8115.2023.03.013

Abstract

Abstract:

Ferroptosis is a form of cell death that results from accumulation of lipid reactive oxygen species, marked by iron-dependent oxidative damage of phospholipids. Accumulation of iron and lipid hydroperoxides are hallmarks of ferroptosis. Diverse biological contexts, including iron handling, redox homeostasis, imbalance of lipid synthesis, participate in ferroptosis. Mechanistically, pathways of ferroptosis regulation involving System X_c^--glutathione (GSH)-glutathione peroxidase 4 (GPX4) axis, coenzyme Q10 (CoQ10)-ferroptosis suppressor protein 1 (FSP1)-ubiquinol axis, GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4)-dihydrofolate reductase (DHFR) axis, dehydrogenase (DHODH)-ubiquinol axis have been discovered. Ferroptosis has been implicated in multiple liver diseases, such as hepatocellular carcinoma, liver ischemia-reperfusion injury, steatohepatitis, liver fibrosis, cirrhosis and liver metabolic diseases. Elucidating its mechanism offers various tractable nodes for therapeutic intervention. Here, we summarize insights into the molecular characteristics, biological processes, regulatory pathways of ferroptosis and its recent advances in the treatment of liver diseases.

Key words: ferroptosis, liver disease, lipid peroxidation

CLC Number:

R575.5

CHEN Chen, CHENG Zhuoan, WANG Cun, XIA Qiang. Research progress in ferroptosis regulation in the treatment of liver diseases[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(3): 365-373.

Figures/Tables 2

TrendMD

References 67

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Inducer	Target	Inhibitor	Target
RSL3, ML162, ML210, FIN56, FINO₂	GPX4	Iron chelator	Iron toxicity
Erastin, erastin analogs, IKE, Sorafenib, Sulfasalazine, PE, glutamate, IFN-γ	System X_c^-	Ferrostatin-1, liprostatin-1, deuterated PUFAs, MUFAs	Lipid peroxidation
FIN56	CoQ10	Vitamin E, α-tocopherol, RTA	Lipid propagation
BSO	Glutamate-cysteine ligase	Thiazolidinediones	ACSL4
Statins	HMG-CoA	Baicalein, Zileuton	Lipoxygenases
Brequinar	DHODH
iFSP1	FSP1
Artemisinins	Ferritinophagy
Methotrexate	Dihydrofolate reductase

Inducer	Target	Inhibitor	Target
RSL3, ML162, ML210, FIN56, FINO₂	GPX4	Iron chelator	Iron toxicity
Erastin, erastin analogs, IKE, Sorafenib, Sulfasalazine, PE, glutamate, IFN-γ	System X_c^-	Ferrostatin-1, liprostatin-1, deuterated PUFAs, MUFAs	Lipid peroxidation
FIN56	CoQ10	Vitamin E, α-tocopherol, RTA	Lipid propagation
BSO	Glutamate-cysteine ligase	Thiazolidinediones	ACSL4
Statins	HMG-CoA	Baicalein, Zileuton	Lipoxygenases
Brequinar	DHODH
iFSP1	FSP1
Artemisinins	Ferritinophagy
Methotrexate	Dihydrofolate reductase

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