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E2F1-dependent miR-421 regulates mitochondrial fragmentation and myocardial infarction by targeting Pink1

Author

Listed:
  • Kun Wang

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

  • Lu-Yu Zhou

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

  • Jian-Xun Wang

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

  • Yin Wang

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

  • Teng Sun

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

  • Bing Zhao

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

  • Yong-Jie Yang

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

  • Tao An

    (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)

  • Bo Long

    (State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences)

  • Na Li

    (State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences)

  • Cui-Yun Liu

    (State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences)

  • Ying Gong

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

  • Jin-Ning Gao

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

  • Yan-Han Dong

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

  • Jian Zhang

    (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)

  • Pei-Feng Li

    (Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University)

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.

Suggested Citation

  • Kun Wang & Lu-Yu Zhou & Jian-Xun Wang & Yin Wang & Teng Sun & Bing Zhao & Yong-Jie Yang & Tao An & Bo Long & Na Li & Cui-Yun Liu & Ying Gong & Jin-Ning Gao & Yan-Han Dong & Jian Zhang & Pei-Feng Li, 2015. "E2F1-dependent miR-421 regulates mitochondrial fragmentation and myocardial infarction by targeting Pink1," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8619
    DOI: 10.1038/ncomms8619
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