Homeostatic Functions of BCL-2 Proteins beyond Apoptosis

  • Nika N. Danial
  • Alfredo Gimenez-Cassina
  • Daniel Tondera
Part of the Advances in Experimental Medicine and Biology book series (volume 687)


Since its introduction in 1930 by physiologist Walter Bradford Cannon, the concept of homeostasis remains the cardinal tenet of biologic regulation. Cells have evolved a highly integrated network of control mechanisms, including positive and negative feedback loops, to safeguard homeostasis in face of a wide range of stimuli. Such control mechanisms ultimately orchestrate cell death, division and repair in a manner concordant with cellular energy and ionic balance to achieve proper biologic fitness. The interdependence of these homeostatic pathways is also evidenced by shared control points that decode intra- and extracellular cues into defined effector responses.

As critical control points of the intrinsic apoptotic pathway, the BCL-2 family of cell death regulators plays an important role in cellular homeostasis.1, 2, 3 The different anti- and pro-apoptotic members of this family form a highly selective network of functional interactions that ultimately governs the permeabilization of the mitochondrial outer membrane and subsequent release of apoptogenic factors such as cytochrome c.4 The advent of loss- and gain-of-function genetic models for the various BCL-2 family proteins has not only provided important insights into apoptosis mechanisms but also uncovered unanticipated roles for these proteins in other physiologic pathways beyond apoptosis (Fig. 1). Here, we turn our attention to these alternative cellular functions for BCL-2 proteins. We begin with a brief introduction of the cast of characters originally known for their capacity to regulate apoptosis and continue to highlight recent advances that have shaped and reshaped our views on their physiologic relevance in integration of apoptosis with other homeostatic pathways.
Figure 1.

Physiologic pathways regulated by BCL-2 family proteins.


Endoplasmic Reticulum Stress Proliferate Cell Nuclear Antigen Unfold Protein Response Mitochondrial Outer Membrane Mitochondrial Dynamic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  • Nika N. Danial
    • 1
    • 2
  • Alfredo Gimenez-Cassina
    • 1
    • 2
  • Daniel Tondera
    • 1
    • 2
  1. 1.Department of PathologyHarvard Medical SchoolBostonUSA
  2. 2.Department of Cancer BiologyDana-Farber Cancer InstituteBostonUSA

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