The Emerging Role of Ferroptosis in Various Chronic Liver Diseases: Opportunity or Challenge

Abstract

Ferroptosis is a recently identified iron-dependent form of intracellular lipid peroxide accumulation-mediated cell death. Different from other types of cell death mechanisms, it exhibits distinct biological and morphological features characterized by the loss of lipid peroxidase repair activity caused by glutathione peroxidase 4, the presence of redox-active iron, and the oxidation of phospholipids-containing polyunsaturated fatty acids. In recent years, studies have shown that ferroptosis plays a key role in various liver diseases such as alcoholic liver injury, non-alcoholic steatohepatitis, liver cirrhosis, and liver cancer. However, the mechanism of ferroptosis and its regulation on chronic liver disease are controversial among different types of cells in the liver. Herein, we summarize the current studies on mechanism of ferroptosis in chronic liver disease, aiming to outline the blueprint of ferroptosis as an effective option for chronic liver disease therapy.

Keywords:

• ferroptosis
• iron metabolism
• liver disease
• oxidative stress
• cell death

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

This research was supported by a grant from Zhejiang Province Public Welfare Fund Research Project (LGD22H030007), and Open Fund of Zhejiang Provincial Key Laboratory of Precision Diagnosis, Treatment and Translation of Chronic Liver Diseases (No.2020E10014-003 and No.2020E10014-007), and the Wenzhou Science and Technology Bureau basic medical and health science and technology projects (No. Y20210147 and No. 2021Y1691).