TY - JOUR
T1 - Regulation of autophagy by Beclin 1 in the heart
AU - Maejima, Yasuhiro
AU - Isobe, Mitsuaki
AU - Sadoshima, Junichi
N1 - Funding Information:
The authors thank Daniela Zablocki for critical reading of the manuscript. This work was supported in part by U.S. Public Health Service Grants HL67724 , HL91469 , HL102738 , HL112330 and AG23039 (JS). This work is also supported by the Fondation Leducq Transatlantic Network of Excellence (JS), JSPS KAKENHI Grant-in-Aid for Scientific Research (C) 26461126 (YM), American Heart Association Scientist Development Grant 12SDG12070262 (YM) and JSPS KAKENHI Grant-in-Aid for Exploratory Research 26670399 & Scientific Research (B) 15H04817 (MI).
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Dysregulation of autophagy in cardiomyocytes is implicated in various heart disease conditions. Beclin 1, a mammalian ortholog of yeast Atg6 and a core component of the autophagy machinery, plays a central role in the regulation of autophagy through activation of Vps34. Beclin 1's ability to activate Vps34 is tightly regulated via transcriptional regulation, miRNA, post-translational modification, and interaction with Beclin 1 binding proteins. Of these mechanisms, binding of Beclin 1 with Bcl-2 family proteins (Bcl-2/XL) that negatively regulate autophagy activity has been shown to be both positively and negatively regulated by various kinases, including DAPK, ROCK1, Mst1 and JNK1, in response to external stimuli. Beclin 1's interaction with Bcl-2/XL also secondarily affects apoptosis through regulation of pro-apoptotic BH3 domain containing proteins. Thus, modulation of Beclin 1 significantly influences both autophagy and apoptosis, thereby deeply affecting the survival and death of cardiomyocytes in the heart. In this review, we discuss the signaling mechanism of autophagy modulation through Beclin 1 and therapeutic potential of Beclin 1 in heart diseases.
AB - Dysregulation of autophagy in cardiomyocytes is implicated in various heart disease conditions. Beclin 1, a mammalian ortholog of yeast Atg6 and a core component of the autophagy machinery, plays a central role in the regulation of autophagy through activation of Vps34. Beclin 1's ability to activate Vps34 is tightly regulated via transcriptional regulation, miRNA, post-translational modification, and interaction with Beclin 1 binding proteins. Of these mechanisms, binding of Beclin 1 with Bcl-2 family proteins (Bcl-2/XL) that negatively regulate autophagy activity has been shown to be both positively and negatively regulated by various kinases, including DAPK, ROCK1, Mst1 and JNK1, in response to external stimuli. Beclin 1's interaction with Bcl-2/XL also secondarily affects apoptosis through regulation of pro-apoptotic BH3 domain containing proteins. Thus, modulation of Beclin 1 significantly influences both autophagy and apoptosis, thereby deeply affecting the survival and death of cardiomyocytes in the heart. In this review, we discuss the signaling mechanism of autophagy modulation through Beclin 1 and therapeutic potential of Beclin 1 in heart diseases.
KW - Apoptosis
KW - Autophagy
KW - Bcl-2 family proteins
KW - Beclin 1
KW - Phosphorylation
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U2 - 10.1016/j.yjmcc.2015.10.032
DO - 10.1016/j.yjmcc.2015.10.032
M3 - Review article
C2 - 26546165
AN - SCOPUS:84962920372
SN - 0022-2828
VL - 95
SP - 19
EP - 25
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
ER -