title: 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 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.
authors.affiliation: Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Hsiang-Chun
authors.initials: HC
authors.lastname: Chang
authors.affiliation: Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Rongxue
authors.initials: R
authors.lastname: Wu
authors.affiliation: Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Shang
authors.affiliation: Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sato
authors.affiliation: Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Chen
authors.affiliation: Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Shapiro
authors.affiliation: Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Thakur
authors.affiliation: Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Konrad T
authors.initials: KT
authors.lastname: Sawicki
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Sathyamangla V N
authors.initials: SV
authors.lastname: Prasad
authors.affiliation: Feinberg Cardiovascular Research Institute (FCVRI), Northwestern University Feinberg School of Medicine, Chicago, IL, USA h-ardehali@northwestern.edu.
authors.forename: Hossein
authors.initials: H
authors.lastname: Ardehali
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D007501:Iron
keywords: heart failure; iron; ischemia; ischemia/reperfusion; mitochondria