title: E2F1-dependent miR-421 regulates mitochondrial fragmentation and myocardial infarction by targeting Pink1.
abstract: Mitochondrial fragmentation plays an important role in the progression of cardiac diseases, such as myocardial infarction and heart failure. Mitochondrial network is controlled by many factors in different cell types. Here we show that the interplay between E2F1, miR-421 and Pink1 regulates mitochondrial morphology and cardiomyocyte cell death. Pink1 reduces mitochondrial fragmentation and protects cardiomyocyte from apoptosis. On the other hand, miR-421 promotes cardiomyocyte mitochondrial fragmentation, apoptosis and myocardial infarction by suppressing Pink1 translation. Finally, we show that transcription factor E2F1 activates miR-421 expression. Knocking down E2F1 suppresses mitochondrial fragmentation, apoptosis and myocardial infarction by affecting miR-421 levels. Collectively, these data identify the E2F1/miR-421/Pink axis as a regulator of mitochondrial fragmentation and cardiomyocyte apoptosis, and suggest potential therapeutic targets in treatment of cardiac diseases.
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Lu-Yu
authors.initials: LY
authors.lastname: Zhou
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Jian-Xun
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Sun
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Heart Failure center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China.
authors.forename: Tao
authors.initials: T
authors.lastname: An
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Long
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Cui-Yun
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Jin-Ning
authors.initials: JN
authors.lastname: Gao
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Yan-Han
authors.initials: YH
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Heart Failure center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Pei-Feng
authors.initials: PF
authors.lastname: Li
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D047369:Chromatin Immunoprecipitation; D050687:E2F1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000255:Adenosine Triphosphate; D050687:E2F1 Transcription Factor; D035683:MicroRNAs; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase; C493754:E2f1 protein, mouse; C000606652:MIRN421 microRNA, mouse