Larger than life: Mitochondria and the Bcl-2 family

The intrinsic pathway of apoptosis relies on mitochondrial membrane permeabilization, with Bcl-2 proteins serving as its master regulators. They form a complex network of interactions both within the family and with multiple cellular factors outside the family. The understanding of the processes that regulate mitochondrial breach, and mechanisms that direct the pro- and anti-apoptotic functions of Bcl-2 proteins, should assist the development of novel anticancer therapies. Thus, it is of no surprise that research in the field is gaining momentum. In this review we outline the current concepts on regulatory circuits governing mitochondrial rupture and action of Bcl-2 proteins during cell death, and how this burgeoning knowledge is being translated into the clinics with the hope to combat cancer.