Bax, Bak and Bid: key mediators of apoptosis

The Bcl-2 family of proteins contains both pro- and antiapoptotic members
that play an orchestrated role in the control of the intrinsic and, in
some cell types, the extrinsic pathways that regulate apoptosis. In this
chapter we review three of the main proapoptotic family members that
exert their functions at the surface of intracellular membranes, notably
the outer mitochondrial membrane. Bax and Bak are multidomain proteins
whose activities are regulated via interactions with other pro- and
antiapoptotic family members, and which may also trigger mitochondrial
disruption directly. In addition, we discuss the emerging role of Bax in
mitochondrial fission and fusion. The third protein we review is the
BH3-only protein Bid, a molecular connector between the intrinsic and
extrinsic apoptosis pathways that activates Bax and Bak. Associations of
Bax, Bak and/or Bid expression and function with cancer progression
and drug responsiveness are also addressed together with the potential
therapeutic opportunities revealed by understanding their regulation.