非表示:
キーワード:
Bcl-2; cell death; membrane curvature; MICOS; superresolution
microscopy
要旨:
The Bcl-2 family proteins Bax and Bak are essential for the
execution of many apoptotic programs. During apoptosis, Bax
translocates to the mitochondria and mediates the permeabilization
of the outer membrane, thereby facilitating the release of
pro-apoptotic proteins. Yet the mechanistic details of the Baxinduced
membrane permeabilization have so far remained
elusive. Here, we demonstrate that activated Bax molecules,
besides forming large and compact clusters, also assemble,
potentially with other proteins including Bak, into ring-like structures
in the mitochondrial outer membrane. STED nanoscopy
indicates that the area enclosed by a Bax ring is devoid of mitochondrial
outer membrane proteins such as Tom20, Tom22, and
Sam50. This strongly supports the view that the Bax rings
surround an opening required for mitochondrial outer membrane
permeabilization (MOMP). Even though these Bax assemblies may
be necessary for MOMP, we demonstrate that at least in Drp1
knockdown cells, these assemblies are not sufficient for full cytochrome
c release. Together, our super-resolution data provide
direct evidence in support of large Bax-delineated pores in the
mitochondrial outer membrane as being crucial for Bax-mediated
MOMP in cells.
