Question

How do Bcl-2 family members regulate apoptosome formation

Answer 1

Apoptosis is an essential physiological process for the selective elimination of cells, which is involved in a variety of biological events

The Bcl‐2 family is the best characterized protein family involved in the regulation of apoptotic cell death, consisting of anti‐apoptotic and pro‐apoptotic members. The anti‐apoptotic members of this family, such as Bcl‐2 and Bcl‐xL, prevent apoptosis either by sequestering proforms of death‐driving cysteine proteases called caspases (a complex called the apoptosome) or by preventing the release of mitochondrial apoptogenic factors such as cytochrome c and AIF (apoptosis‐inducing factor) into the cytoplasm. After entering the cytoplasm, cytochrome c and AIF directly activate caspases that cleave a set of cellular proteins to cause apoptotic changes

In contrast, pro‐apoptotic members of this family, such as Bax and Bak, trigger the release of caspases from death antagonists via heterodimerization and also by inducing the release of mitochondrial apoptogenic factors into the cytoplasm via acting on mitochondrial permeability transition pore, thereby leading to caspase activation. Thus, the Bcl‐2 family of proteins acts as a critical life–death decision point within the common pathway of apoptosis.

The Bcl‐2 family of proteins comprises the anti‐apoptotic and pro‐apoptotic molecules. The Bcl‐2 family is classified into the following three subfamilies depending on the homology and functions of each protein

(i) A subfamily including Bcl‐2, Bcl‐xL and Bcl‐w, all of which exert anti‐cell death activity and share sequence homology particularly within four regions, BH (Bcl‐2 homology)1 through BH4

(ii) A subfamily represented by Bax and Bak, which share sequence homology at BH1, BH2 and BH3 but not at BH4, although significant homology at BH4 is also noticed in some members. All these proteins exert pro‐apoptotic activity

(iii) A subfamily including Bik and Bid, all of which are pro‐apoptotic and share sequence homology only within BH3 (for this reason, the members of this subfamily are called BH3 proteins).