Reduction in mitochondrial iron alleviates cardiac damage during injury
Abstract Excess cellular iron increases reactive oxygen species (ROS) production and causes cellular damage. Mitochondria are the major site of iron metabolism and ROS production; however, few studies have investigated the role of mitochondrial iron in the development of cardiac disorders, such as i...
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| Format: | Article |
| Language: | English |
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Springer Nature
2016-02-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201505748 |
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| _version_ | 1849342017768783872 |
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| author | Hsiang‐Chun Chang Rongxue Wu Meng Shang Tatsuya Sato Chunlei Chen Jason S Shapiro Ting Liu Anita Thakur Konrad T Sawicki Sathyamangla VN Prasad Hossein Ardehali |
| author_facet | Hsiang‐Chun Chang Rongxue Wu Meng Shang Tatsuya Sato Chunlei Chen Jason S Shapiro Ting Liu Anita Thakur Konrad T Sawicki Sathyamangla VN Prasad Hossein Ardehali |
| author_sort | Hsiang‐Chun Chang |
| collection | DOAJ |
| description | Abstract Excess cellular iron increases reactive oxygen species (ROS) production and causes cellular damage. Mitochondria are the major site of iron metabolism and ROS production; however, few studies have investigated the role of mitochondrial iron in the development of cardiac disorders, such as ischemic heart disease or cardiomyopathy (CM). We observe increased mitochondrial iron in mice after ischemia/reperfusion (I/R) and in human hearts with ischemic CM, and hypothesize that decreasing mitochondrial iron protects against I/R damage and the development of CM. Reducing mitochondrial iron genetically through cardiac‐specific overexpression of a mitochondrial iron export protein or pharmacologically using a mitochondria‐permeable iron chelator protects mice against I/R injury. Furthermore, decreasing mitochondrial iron protects the murine hearts in a model of spontaneous CM with mitochondrial iron accumulation. Reduced mitochondrial ROS that is independent of alterations in the electron transport chain's ROS producing capacity contributes to the protective effects. Overall, our findings suggest that mitochondrial iron contributes to cardiac ischemic damage, and may be a novel therapeutic target against ischemic heart disease. |
| format | Article |
| id | doaj-art-e6b2dfb41f894ce0b3d39c6f95f0a18b |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-e6b2dfb41f894ce0b3d39c6f95f0a18b2025-08-20T03:43:30ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-02-018324726710.15252/emmm.201505748Reduction in mitochondrial iron alleviates cardiac damage during injuryHsiang‐Chun Chang0Rongxue Wu1Meng Shang2Tatsuya Sato3Chunlei Chen4Jason S Shapiro5Ting Liu6Anita Thakur7Konrad T Sawicki8Sathyamangla VN Prasad9Hossein Ardehali10Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of MedicineFeinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of MedicineFeinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of MedicineFeinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of MedicineFeinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of MedicineFeinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of MedicineFeinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of MedicineFeinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of MedicineFeinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of MedicineDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic FoundationFeinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of MedicineAbstract Excess cellular iron increases reactive oxygen species (ROS) production and causes cellular damage. Mitochondria are the major site of iron metabolism and ROS production; however, few studies have investigated the role of mitochondrial iron in the development of cardiac disorders, such as ischemic heart disease or cardiomyopathy (CM). We observe increased mitochondrial iron in mice after ischemia/reperfusion (I/R) and in human hearts with ischemic CM, and hypothesize that decreasing mitochondrial iron protects against I/R damage and the development of CM. Reducing mitochondrial iron genetically through cardiac‐specific overexpression of a mitochondrial iron export protein or pharmacologically using a mitochondria‐permeable iron chelator protects mice against I/R injury. Furthermore, decreasing mitochondrial iron protects the murine hearts in a model of spontaneous CM with mitochondrial iron accumulation. Reduced mitochondrial ROS that is independent of alterations in the electron transport chain's ROS producing capacity contributes to the protective effects. Overall, our findings suggest that mitochondrial iron contributes to cardiac ischemic damage, and may be a novel therapeutic target against ischemic heart disease.https://doi.org/10.15252/emmm.201505748heart failureironischemiaischemia/reperfusionmitochondria |
| spellingShingle | Hsiang‐Chun Chang Rongxue Wu Meng Shang Tatsuya Sato Chunlei Chen Jason S Shapiro Ting Liu Anita Thakur Konrad T Sawicki Sathyamangla VN Prasad Hossein Ardehali Reduction in mitochondrial iron alleviates cardiac damage during injury EMBO Molecular Medicine heart failure iron ischemia ischemia/reperfusion mitochondria |
| title | Reduction in mitochondrial iron alleviates cardiac damage during injury |
| title_full | Reduction in mitochondrial iron alleviates cardiac damage during injury |
| title_fullStr | Reduction in mitochondrial iron alleviates cardiac damage during injury |
| title_full_unstemmed | Reduction in mitochondrial iron alleviates cardiac damage during injury |
| title_short | Reduction in mitochondrial iron alleviates cardiac damage during injury |
| title_sort | reduction in mitochondrial iron alleviates cardiac damage during injury |
| topic | heart failure iron ischemia ischemia/reperfusion mitochondria |
| url | https://doi.org/10.15252/emmm.201505748 |
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