TY - JOUR
T1 - Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy
AU - Pattingre, Sophie
AU - Tassa, Amina
AU - Qu, Xueping
AU - Garuti, Rita
AU - Xiao, Huan Liang
AU - Mizushima, Noboru
AU - Packer, Milton
AU - Schneider, Michael D.
AU - Levine, Beth
N1 - Funding Information:
This work was supported by NIH grants R01 AI151367, AI44157, CA084254, and CA109618 and an American Cancer Society Grant ACS RSG 98-339 to B.L. We thank Yajuan Liu and Jie Yu for excellent technical assistance; Christopher Gilpin and Tom Januszewski for assistance with electron microscopy; David Andrews, Jonathan Backer, Marie-Therese Dimanche-Boitrel, Lewis Cantley, Patrice Codogno, and Tamotsu Yoshimori for providing reagents; and Frederick Scott and Renee Talley for administrative assistance.
PY - 2005/9/23
Y1 - 2005/9/23
N2 - Apoptosis and autophagy are both tightly regulated biological processes that play a central role in tissue homeostasis, development, and disease. The anti-apoptotic protein, Bcl-2, interacts with the evolutionarily conserved autophagy protein, Beclin 1. However, little is known about the functional significance of this interaction. Here, we show that wild-type Bcl-2 antiapoptotic proteins, but not Beclin 1 binding defective mutants of Bcl-2, inhibit Beclin 1-dependent autophagy in yeast and mammalian cells and that cardiac Bcl-2 transgenic expression inhibits autophagy in mouse heart muscle. Furthermore, Beclin 1 mutants that cannot bind to Bcl-2 induce more autophagy than wild-type Beclin 1 and, unlike wild-type Beclin 1, promote cell death. Thus, Bcl-2 not only functions as an antiapoptotic protein, but also as an antiautophagy protein via its inhibitory interaction with Beclin 1. This antiautophagy function of Bcl-2 may help maintain autophagy at levels that are compatible with cell survival, rather than cell death.
AB - Apoptosis and autophagy are both tightly regulated biological processes that play a central role in tissue homeostasis, development, and disease. The anti-apoptotic protein, Bcl-2, interacts with the evolutionarily conserved autophagy protein, Beclin 1. However, little is known about the functional significance of this interaction. Here, we show that wild-type Bcl-2 antiapoptotic proteins, but not Beclin 1 binding defective mutants of Bcl-2, inhibit Beclin 1-dependent autophagy in yeast and mammalian cells and that cardiac Bcl-2 transgenic expression inhibits autophagy in mouse heart muscle. Furthermore, Beclin 1 mutants that cannot bind to Bcl-2 induce more autophagy than wild-type Beclin 1 and, unlike wild-type Beclin 1, promote cell death. Thus, Bcl-2 not only functions as an antiapoptotic protein, but also as an antiautophagy protein via its inhibitory interaction with Beclin 1. This antiautophagy function of Bcl-2 may help maintain autophagy at levels that are compatible with cell survival, rather than cell death.
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U2 - 10.1016/j.cell.2005.07.002
DO - 10.1016/j.cell.2005.07.002
M3 - Article
C2 - 16179260
AN - SCOPUS:25144457455
SN - 0092-8674
VL - 122
SP - 927
EP - 939
JO - Cell
JF - Cell
IS - 6
ER -