Death by association: BH3 domain-only proteins and liver injury

Apoptosis, a prominent form of cell death, is a prime feature of many acute and chronic liver diseases. Apoptosis requires mitochondrial dysfunction, which is regulated by proteins of the Bcl-2 family. Whether or not a cell should live or die is controlled by the interaction of multidomain Bcl-2 proteins with proapoptotic BH3 domain-only proteins of this family. Current models suggest multidomain, antiapoptotic Bcl-2 proteins prevent mitochondrial dysfunction by sequestering and/or preventing activation of its proapoptotic relatives. BH3-only proteins initiate cell death by neutralizing and or ligating multidomain prosurvival Bcl-2 proteins. Thus BH3 domain-only proteins are paramount in the apoptotic process as exemplified by the role of the BH3 domain-only protein Bid in liver injury. In this concise review, we will focus on how these BH3 domain-only proteins are regulated in the cell, their association with the Bcl-2 family of proteins, and finally, current information regarding their involvement in liver cell apoptosis and injury.