Ferroptosis in liver disease: new insights into disease mechanisms
Abstract 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-10-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-021-00660-4 |
| _version_ | 1818930276886118400 |
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| author | Jing Wu Yi Wang Rongtao Jiang Ran Xue Xuehong Yin Muchen Wu Qinghua Meng |
| author_facet | Jing Wu Yi Wang Rongtao Jiang Ran Xue Xuehong Yin Muchen Wu Qinghua Meng |
| author_sort | Jing Wu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-20T03:58:08Z |
| format | Article |
| id | doaj.art-8bc502c0720345aca15edd4a399ded9f |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-20T03:58:08Z |
| publishDate | 2021-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-8bc502c0720345aca15edd4a399ded9f2022-12-21T19:54:15ZengNature Publishing GroupCell Death Discovery2058-77162021-10-01711910.1038/s41420-021-00660-4Ferroptosis in liver disease: new insights into disease mechanismsJing Wu0Yi Wang1Rongtao Jiang2Ran Xue3Xuehong Yin4Muchen Wu5Qinghua Meng6Department of Medical Oncology, Beijing You-An Hospital, Capital Medical UniversityState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of LifeomicsBrainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of SciencesKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & InstituteDepartment of Medical Oncology, Beijing You-An Hospital, Capital Medical UniversityDepartment of Medical Oncology, Beijing You-An Hospital, Capital Medical UniversityDepartment of Medical Oncology, Beijing You-An Hospital, Capital Medical UniversityAbstract 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.https://doi.org/10.1038/s41420-021-00660-4 |
| spellingShingle | Jing Wu Yi Wang Rongtao Jiang Ran Xue Xuehong Yin Muchen Wu Qinghua Meng Ferroptosis in liver disease: new insights into disease mechanisms Cell Death Discovery |
| title | Ferroptosis in liver disease: new insights into disease mechanisms |
| title_full | Ferroptosis in liver disease: new insights into disease mechanisms |
| title_fullStr | Ferroptosis in liver disease: new insights into disease mechanisms |
| title_full_unstemmed | Ferroptosis in liver disease: new insights into disease mechanisms |
| title_short | Ferroptosis in liver disease: new insights into disease mechanisms |
| title_sort | ferroptosis in liver disease new insights into disease mechanisms |
| url | https://doi.org/10.1038/s41420-021-00660-4 |
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