Cytosolic Pcd Pathway

Induction of PCD might also occur independently of Mt depolarization (47) by primarily cytosolic mechanisms. One key component of the cell death machinery, Apaf-1, in the presence of dATP forms a complex with cytochrome-c and caspase-9 (the apoptosome) (13,48,49). Selective binding of caspase-9 to Apaf-1 results in caspase-9-dependent hierarchical activation of caspases-2, -3, -6, -7, -8, and -10, resulting ultimately in DNA fragmentation seen in apoptosis (50-53). In turn, caspase-3 activates caspase-2, -6, -8, and -10 and amplifies caspase-9 cleavage (50). In contrast, BCL-2 and BCL-xL complex with Apaf-1 and caspase-9 through different binding sites to form a ternary complex (48) that inhibits cleavage of downstream caspases (48) and serve to inhibit PCD.

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