The Mitochondrial Pathway of Apoptosis Part II: The BCL-2 Protein Family

CONTROLLING MITOCHONDRIAL OUTER MEMBRANE PERMEABILIZATION

We are now near the top of the mitochondrial pathway of apoptosis, at the point before the mitochondrial outer membrane permeabilizes to release proteins such as cytochrome c into the cytosol. This is where the major decisions are made that determine whether a cell will die by engaging this pathway. And these decisions depend on interactions among members of the BCL-2 family of proteins.

The BCL-2 proteins, named for the first family member to be described (B cell lymphoma-2), are a collection of related molecules found throughout the animal kingdom. They share only limited sequence similarity, except in short regions called BCL-2 homology (BH) domains, and can be grouped according to which of these domains they carry and, as we will see, by their functions. A list of several BCL-2 proteins in mammals and their BH domains is shown in Figure 1.