Bcl-2 Proteins: Regulators of Apoptosis or of Mitochondrial Homeostasis?

Nat Cell Biol. 1999 Dec;1(8):E209-16. doi: 10.1038/70237.


Programmed cell death (apoptosis) is used by multicellular organisms during development and to maintain homeostasis within mature tissues. One of the first genes shown to regulate apoptosis was bcl-2. Subsequently, a number of Bcl-2-related proteins have been identified. Despite overwhelming evidence that Bcl-2 proteins are evolutionarily conserved regulators of apoptosis, their precise biochemical function remains controversial. Three biochemical properties of Bcl-2 proteins have been identified: their ability to localize constitutively and/or inducibly to the outer mitochondrial, outer nuclear and endoplasmic reticular membranes, their ability to form heterodimers with proteins bearing an amphipathic helical BH3 domain, and their ability to form ion-conducting channels in synthetic membranes. The discovery that mitochondria can play a key part in the induction of apoptosis has focused attention on the role that Bcl-2 proteins may have in regulating either mitochondrial physiology or mitochondria-dependent caspase activation. Here we attempt to synthesize our current understanding of the part played by mitochondria in apoptosis with a consideration of how Bcl-2 proteins might control cell death through an ability to regulate mitochondrial physiology.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Caspases / metabolism
  • Cytochrome c Group / metabolism
  • Homeostasis*
  • Humans
  • Ion Channels*
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Mitochondria / enzymology
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Membrane Transport Proteins
  • Necrosis
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*


  • Cytochrome c Group
  • Ion Channels
  • Membrane Proteins
  • Mitochondrial Membrane Transport Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • mitochondrial permeability transition pore
  • Caspases