The role of NCOA4-mediated ferritinophagy in the ferroptosis of hepatocytes: A mechanistic viewpoint

This paper focuses on the mechanism underlying nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and subsequent hepatocyte ferroptosis. Iron is a pivotal trace element, but excessive iron deposition can lead to liver injury. Ferroptosis is a recognized, iron-dependent mode of programmed cell death that plays an important role in various liver diseases. NCOA4 is a key molecule mediating the selective autophagic degradation of ferritin. It affects ferroptosis by regulating intracellular free iron levels. NCOA4 expression is regulated by various factors, including cellular iron levels and oxidative stress. It was demonstrated that inhibition of NCOA4 can reduce iron-mediated cell death and mitigate liver damage, suggesting that NCOA4 may be a potential target for the prevention and treatment of liver diseases. Further in-depth studies of the molecular mechanism of NCOA4-mediated ferritinophagy and its relationship with iron-induced cell death can provide novel ideas for the diagnosis and treatment of liver diseases. The deficiency or abnormal expression of NCOA4 is closely associated with ferroptosis in a variety of liver diseases, including non-alcoholic fatty liver disease, alcoholic liver disease, drug-induced liver injury, and liver fibrosis. Future studies should focus on elucidating the dynamic changes in the NCOA4 regulatory network during specific pathological processes. This strategy can lay the foundation for drug development.