pro-apoptotic factors from mitochondria. Recently, Bcl-2 has been
shown to also inhibit autophagy [32, 35] and ACD [36]. It has
been suggested that the anti-autophagy function of Bcl-2 may help
maintain autophagy at levels that are compatible with cell survival,
rather than cell death [35]. However, the effect of Bcl-2 on
autophagy is controversial as it has also been reported to sensitize
cells to autophagy and permit autophagy to develop through inhibition
of apoptosis [33, 37]. Bcl-2 inhibition of autophagy is mediated
through its interaction with Beclin 1 [35]. Beclin 1 was the
first identified mammalian autophagy gene product and plays an
essential role in autophagosome formation [39]. However, it was
originally identified in a screen for Bcl-2-interacting proteins [39].
Recently, Beclin 1 has been shown to be a novel BH3-only protein
and to interact with a number of anti-apoptotic Bcl-2 family members
including Bcl-2, Bcl-xL, Bcl-w and Mcl-1 [40–43]. Thus, one
possible scenario is that a Bcl-2:Beclin 1 rheostat acts as a switch
between autophagy and apoptosis.