Logical complexity of Bcl-2 family proteins function in the intrinsic apoptosis

Abstract

Apoptosis (type of programmed cell death) is an active process of cellular self-destruction in multicellular organisms. It is characterized by distinctive histomorphological, biochemical, and molecular features. Multiple cellular pathways trigger apoptosis, two of them are the best known: intrinsic and extrinsic. Multiple cellular signals and interactions can influence the course of apoptotic pathways. Bcl-2 family proteins play a key role in regulatory mechanisms of intrinsic apoptosis. Mitochondrial outer membrane permeabilization (MOMP) is an essential step for intrinsic apoptosis that is controlled by pro-apoptotic and anti-apoptotic members of Bcl-2 protein family. Pro-apoptotic effector proteins Bax and Bak represent the only Bcl-2 proteins inducing formation of MOMP, whose pores facilitate the subsequent releasing of several pro-apoptotic proteins from mitochondrial intermembrane space into cytosol. These proteins initiate a caspase cascade, resulting in rapid elimination of the doomed cells.