Reduction in mitochondrial iron alleviates cardiac damage during injury
| Autor: | Meng Shang, Sathyamangla Vn Prasad, Jason S. Shapiro, Anita Thakur, Tatsuya Sato, Ting Liu, Rongxue Wu, Hossein Ardehali, Hsiang-Chun Chang, Konrad T Sawicki, Chunlei Chen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS Iron Ischemia Cardiomyopathy heart failure Myocardial Reperfusion Injury ischemia Mitochondrion Biology Cardiovascular System 03 medical and health sciences medicine Animals Humans Research Articles chemistry.chemical_classification Reactive oxygen species Metabolism medicine.disease ischemia/reperfusion Electron transport chain Mitochondria Cell biology Mice Inbred C57BL Disease Models Animal 030104 developmental biology chemistry Biochemistry Heart failure Molecular Medicine Cardiomyopathies Reactive Oxygen Species Research Article |
| Zdroj: | EMBO Molecular Medicine |
| ISSN: | 1757-4684 1757-4676 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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