title: Mitochondrial ferritin protects the murine myocardium from acute exhaustive exercise injury.
abstract: Mitochondrial ferritin (FtMt) is a mitochondrially localized protein possessing ferroxidase activity and the ability to store iron. FtMt overexpression in cultured cells protects against oxidative damage by sequestering redox-active, intracellular iron. Here, we found that acute exhaustive exercise significantly increases FtMt expression in the murine heart. FtMt gene disruption decreased the exhaustion exercise time and altered heart morphology with severe cardiac mitochondrial injury and fibril disorganization. The number of apoptotic cells as well as the levels of apoptosis-related proteins was increased in the FtMt-/-mice, though the ATP levels did not change significantly. Concomitant to the above was a high 'uncommitted' iron level found in the FtMt-/-group when exposed to acute exhaustion exercise. As a result of the increase in catalytic metal, reactive oxygen species were generated, leading to oxidative damage of cellular components. Taken together, our results show that the absence of FtMt, which is highly expressed in the heart, increases the sensitivity of mitochondria to cardiac injury via oxidative stress.
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Wu
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Chang
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.|The 3rd Hospital of Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Peina
authors.initials: P
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Guofen
authors.initials: G
authors.lastname: Gao
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Yan-Zhong
authors.identifier: 0000-0002-6386-9649
authors.initials: YZ
authors.lastname: Chang
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism*; D017353:Gene Deletion; D015151:Immunoblotting; D007501:Iron / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal
chemical_list: D002316:Cardiotonic Agents; D005293:Ferritins; D007501:Iron; D002118:Calcium