Ferroptosis in liver disease: new insights into disease mechanisms

• Published in: Cell death discovery Vol. 7; no. 1; p. 276
• Main Authors: Wu, Jing, Wang, Yi, Jiang, Rongtao, Xue, Ran, Yin, Xuehong, Wu, Muchen, Meng, Qinghua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.10.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 692/699/1503/1607; 692/699/1503/1607/1610/4029; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Cycle Analysis; Cell death; Cytosol; Fatty liver; Ferroptosis; GTP cyclohydrolase; Hemochromatosis; Hepatocellular carcinoma; Ischemia; Life Sciences; Lipid peroxidation; Liver diseases; Mitochondria; Molecular modelling; p53 Protein; Pathophysiology; Reperfusion; Review; Review Article; Stem Cells; Therapeutic targets
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-021-00660-4

Characterized by excessive iron accumulation and lipid peroxidation, ferroptosis is a novel form of iron-dependent cell death, which is morphologically, genetically, and biochemically distinct from other well-known cell death. In recent years, ferroptosis has been quickly gaining attention in the field of liver diseases, as the liver is predisposed to oxidative injury and generally, excessive iron accumulation is a primary characteristic of most major liver diseases. In the current review, we first delineate three cellular defense mechanisms against ferroptosis (GPx4 in the mitochondria and cytosol, FSP1 on plasma membrane, and DHODH in mitochondria), along with four canonical modulators of ferroptosis (system Xc − , nuclear factor erythroid 2-related factor 2, p53, and GTP cyclohydrolase-1). Next, we review recent progress of ferroptosis studies delineating molecular mechanisms underlying the pathophysiology of several common liver diseases including ischemia/reperfusion-related injury (IRI), nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), hemochromatosis (HH), drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). Furthermore, we also highlight both challenges and promises that emerged from recent studies that should be addressed and pursued in future investigations before ferroptosis regulation could be adopted as an effective therapeutic target in clinical practice.