How the two killer proteins Bax and Bak form the putative “apoptotic pore” that is responsible for irrevocably damaging mitochondria leading to cell death during apoptosis is considered the “holy grail” of apoptosis research. Indeed, even whether Bax and Bak form a pore remains contentious largely due to the failure to detect such structures in cells or mitochondria. Two new super‐resolution microscopy studies in this issue of The EMBO Journal now provide tantalising evidence of ring‐like “apoptotic pores” on mitochondria of dying cells and provide new insight into how Bax and Bak bring about a cell's demise.
See also: L Große et al (February 2016) and
R Salvador‐Gallego et al (February 2016)
Bax and Bak are members of the Bcl‐2 family of proteins and the critical executioners of the intrinsic pathway of apoptosis (Wei et al, 2001). Following reception of an apoptotic stress, interaction with another subclass of the Bcl‐2 family, the BH3‐only proteins, induces a drastic change in conformation of Bax and Bak. These activated conformations are then compatible for self‐association on the mitochondrial outer membrane. A long‐held notion is that these oligomeric proteins form pores that damage the outer membrane of mitochondria. The “apoptotic pore” then acts as a conduit for a variety of intermembrane space proteins including cytochrome c and Smac/DIABLO that trigger the final proteolytic destruction and packaging of the cell during apoptosis. Recent biochemical and structural advances have provided much needed insight into how these important proteins morph into their deadly form and undergo the initial steps in oligomerisation (Dewson et al, 2008, 2012; Bleicken et al, 2010; Oh et al, 2010; Zhang et al, …
Subscribers, please sign in with your username and password.