Mitochondria in Apoptosis

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 Apaf-1, 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).

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References:

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