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Programmed cell death, which is termed as apoptosis, is essential
for normal development and maintenance of tissue homeostasis in
multicellular organisms. Aberrant regulation of this pathway is
linked to multiple human diseases, including cancer, autoimmunity,
neurodegenerative disorders and diabetes. Apoptosis is pursued by
two pathways; extrinsic and intrinsic pathway. The intrinsic
pathway of apoptosis mainly relies on mitochondria where Bcl-2
family proteins serve as the master regulators. Mitochondria mainly
execute their function through mitochondrial outer membrane
permeabilization (MOMP). MOMP leads to the release of several
apoptogenic factors from mitochondrial intermembrane space, such as
cytochrome c and Smac/Diablo, into the cytosol that activate
downstream caspase and promote cell death. Bcl-2 family proteins
play key role by regulating MOMP. The complex interaction among
pro-and anti-apoptotic Bcl-2 family members determine the
possibility of MOMP and thereby determine the cellular commitment
to apoptosis. This review focuses on the mitochondrial pathway of
apoptosis, mechanism of MOMP and its regulation by Bcl-2 family
proteins.
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