Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy

Beth Levine, et al. Cell, Vol. 122, 927–939, Sep 2005

Speaker : 張明俐                                          Time : 2005.12.21 13:10 ~ 14:00

Commentator : 徐麗君 老師                        Place : Room 601

Abstract:

Autophagy is an evolutionarily ancient process, conserved from yeast to mammals. The anti-apoptotic protein, Bcl-2, interacts with Beclin 1 the evolutionarily conserved autophagy protein¹. However, little is known about the functional significance of this interaction. In this study, the authors found that the direct interaction between Bcl-2 with Beclin-1 is required because the inhibition is prevented by either mutations in Bcl-2 that block binding to Beclin 1 or mutations in Beclin 1 that block binding to Bcl-2. Bcl-2 regulates autophagy negatively through inhibiting the formation of the autophagy-promoting complex. Furthermore, they found that interaction between endogenous Bcl-2 and endogenous Beclin 1 is a nutrient-dependent manner. For in vivo observation, they used a transgenic mouse model which expressed GFP-LC3, a fluorescent autophagy marker, and human Bcl-2 to measure autophagy phenomenon. As a result, autophagy is inhibited. According to these observations, as a well-known anti-apoptotic protein, Bcl-2 is found to inhibit Beclin 1-dependent autophagy via an interaction with Beclin-1². The mechanism is suggested that could promote autophagy to keep cell in survival rather than death level.

References:

1. Liang, X.H., et al. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J.Virol. 72:8586–8596, 1998

2. Pattingre S., et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927–939, 2005