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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, a
key protein in electron transport, appears to act by forming a multimeric complex with Apaf1, a protease, which in turn activates procaspase 9, and begins a cascade of activation of
downstream caspases. Smac/Diablo is released from the mitochondria and inhibits IAP
(inhibitor of apoptosis) from interacting with caspase 9 leading to apoptosis. Bcl-2 and Bcl-X
can prevent pore formation and 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
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Cai, J., et al., Mitochondrial control of apoptosis: the role of cytochrome c. Biochim. Biophys.
Acta, 1366, 139-149 (1998).
Lee, H., and Wei, Y., Mitochondrial role in life and death of the cell. J. Biomed. Sci., 7, 2-15
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