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Mitochondria in Apoptosis
SIGMA-ALDRICH
Mitochondria in Apoptosis
Increases in cytosolic Ca2+ levels due to activation of ion channel-linked receptors, such as
that for the excitatory amino acid neurotransmitter glutamic acid, can induce permeability
transition (PT) of the mitochondrial membrane. PT constitutes the first rate-limiting event of
the common pathway of apoptosis. Upon PT, apoptogenic factors leak into the cytoplasm
from the mitochondrial intermembrane space. Two such factors, cytochrome c and
apoptosis inducing factor (AIF), begin a cascade of proteolytic activity that ultimately leads
to nuclear damage (DNA fragmentation, DNA mutations) and cell death. Cytochrome c
appears to act by forming multimeric complexes with Apaf-1, which in turn activate
procaspase 9, and begin a cascade of activation of downstream caspases. Bcl-2 can block
the release of cytochrome c from the mitochondria and prevent activation of the caspase
cascade and apoptosis. PT is also related to the mitochondrial generation of reactive oxygen
species which plays a role in the degradation phase of apoptosis (i.e. plasma membrane
alterations).
References
Budihardjo, I., et al., Biochemical pathways of caspase activation during apoptosis. Annu. Rev. Cell Dev. Biol.,
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Susin, S.A., et al., Molecular characterization of mitochondrial apoptosis-inducing factor. Nature, 397, 441-446
(1999).
Cai, J., et al., Mitochondrial control of apoptosis: the role of cytochrome c. Biochim. Biophys. Acta, 1366, 139149 (1998).
Lee, H., and Wei, Y., Mitochondrial role in life and death of the cell. J. Biomed. Sci., 7, 2-15 (2000).