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The multifaceted role of ferroptosis in liver disease

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CELL DEATH AND DIFFERENTIATION
卷 29, 期 3, 页码 467-480

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SPRINGERNATURE
DOI: 10.1038/s41418-022-00941-0

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资金

  1. National Natural Science Foundation of China [31970689, 31930057]
  2. National Key R&D Program of China [2018YFA0507801, 2018YFA0507802]

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Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by excessive lipid peroxidation and is associated with liver diseases. Dysregulated metabolic pathways and impaired iron homeostasis play a role in the progression of liver disease via ferroptosis. Several ferroptosis-associated genes and pathways have been implicated in liver disease. Targeting ferroptosis may have therapeutic potential for managing liver diseases.
Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by excessive lipid peroxidation and associated with a plethora of pathological conditions in the liver. Emerging evidence supports the notion that dysregulated metabolic pathways and impaired iron homeostasis play a role in the progression of liver disease via ferroptosis. Although the molecular mechanisms by which ferroptosis causes disease are poorly understood, several ferroptosis-associated genes and pathways have been implicated in liver disease. Here, we review the physiological role of the liver in processing nutrients, our current understanding of iron metabolism, the characteristics of ferroptosis, and the mechanisms that regulate ferroptosis. In addition, we summarize the role of ferroptosis in the pathogenesis of liver disease, including liver injury, non-alcoholic steatohepatitis, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Finally, we discuss the therapeutic potential of targeting ferroptosis for managing liver disease.

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