期刊
EMBO MOLECULAR MEDICINE
卷 8, 期 3, 页码 247-267出版社
WILEY
DOI: 10.15252/emmm.201505748
关键词
heart failure; iron; ischemia; ischemia; reperfusion; mitochondria
资金
- Northwestern University Interdepartmental ImmunoBiology Flow Cytometry Core Facility
- Northwestern University Mouse Histology and Phenotyping Laboratory
- Cancer Center Support Grant (NCI) [CA060553]
- NIH [K02 HL107448, R01 HL104181, 1PO1 HL108795, T32GM008152]
- American Heart Association [12PRE12030002]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据