The critical role of autophagy in heart failure

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  • Maejima Yasuhiro
    Department of Cardiovascular Medicine, Tokyo Medical and Dental University

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  • オートファジーの制御異常による心不全発症機構の解明
  • オートファジー ノ セイギョ イジョウ ニ ヨル シンフゼン ハッショウ キコウ ノ カイメイ

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Abstract

<p>Autophagy is an evolutionarily conserved process for degradation of long-lived proteins and organelles that govern a number of cardiac pathologies which cause heart failure. Indeed, recent investigations have uncovered pathways that regulate autophagy in the heart and underlying mechanisms by which alterations in this process affect cardiac function and structure. One of the major roles of autophagy in cardiomyocytes is the intracellular protein quality control (PQC). Impairment of autophagy causes aggregation of damaged and/or misfolded proteins in cardiomyocytes, thereby damaging the cells which, in turn leads to pathological cardiac remodeling. We have shown previously that the molecular mechanism of autophagy suppression in response to cardiac stress. Activation of mammalian Ste20-like kinase 1 (Mst1) by stress causes autophagy suppression below physiological levels and inhibits PQC, which in turn contributes to cardiac dysfunction. Specifically, Mst1 inhibits autophagy through phosphorylation of Beclin1, enhancement of Beclin1-Bcl-2 interaction and suppression of Vps34. Here, I show recent advances in understanding the role of autophagy in pathological cardiac remodeling and discuss the therapeutic potential of modulating autophagy in heart disease.</p>

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