title: miR-361-regulated prohibitin inhibits mitochondrial fission and apoptosis and protects heart from ischemia injury.
abstract: Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Emerging evidences suggest that the abnormal mitochondrial fission participates in pathogenesis of cardiac diseases, including myocardial infarction (MI) and heart failure. However, the molecular components regulating mitochondrial network in the heart remain largely unidentified. Here we report that miR-361 and prohibitin 1 (PHB1) constitute an axis that regulates mitochondrial fission and apoptosis. The results show that PHB1 attenuates mitochondrial fission and apoptosis in response to hydrogen peroxide treatment in cardiomyocytes. Cardiac-specific PHB1 transgenic mice show reduced mitochondrial fission and myocardial infarction sizes after myocardial infarction surgery. MiR-361 is responsible for the dysfunction of PHB1 and suppresses the translation of PHB1. Knockdown of miR-361 reduces mitochondrial fission and apoptosis in vivo and in vitro. MiR-361 cardiac-specific transgenic mice represent elevated mitochondrial fission and myocardial infarction sizes upon myocardial ischemia injury. This study identifies a novel signaling pathway composed of miR-361 and PHB1 that regulates mitochondrial fission program and apoptosis. This discovery will shed new light on the therapy of myocardial infarction and heart failure.
authors.affiliation: 1] Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China [2] Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, China.
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.affiliation: Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Feng
authors.affiliation: 1] Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China [2] Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, China.
authors.forename: L-Y
authors.initials: LY
authors.lastname: Zhou
authors.affiliation: Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 1] Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China [2] Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, China.
authors.forename: P-F
authors.initials: PF
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000235:genetics*; D017202:Myocardial Ischemia / Q000235:genetics* / Q000517:prevention & control; D000091402:Prohibitins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D000091402:Prohibitins; D012097:Repressor Proteins