If cytochrome c is released from mitochondria due to formation of a channel, in the outer mitochondrial membrane during the apoptosis process, it binds to apoptotic protease activating factor-1 (Apaf-1) and ATP, which then bind to pro-caspase-9 creating a protein complex known as
apoptosome (Dejean et al.
In the Intrinsic pathway, the release of cytochrome c from the mitochondria into the cytosol is fundamental to
apoptosome formation and downstream caspase activation.
If cytochrome c is released from mitochondria due to formation of a channel in the outer mitochondrial membrane during the apoptosis process, it binds to apoptotic protease activating factor-1 (Apaf-1) and ATP, which then bind to procaspase-9 creating a protein complex known as
apoptosome (Dejean et al.
In the absence of apoptosis stimulation, intrinsic activation of apoptosis can be achieved by the initiation of caspase 9 and
apoptosome formation which triggers the activation of downstream caspases.
Released cytochrome c into cytosol forms the
apoptosome to activate caspase-9 and caspase-3 (Hetz et al.
After treatment of cells with apoptotic agents including H202, cytochrome c is released from mitochondrial intermembrane space and binds to the apoptosis protease activation factor (APAf-1) to forms an
apoptosome complex.
The mitochondria-mediated pathway involves the release of cytochrome c, and then followed by the formation of
apoptosome, a 140-kDa cytoplasmic complex, consisting of Apaf-1 (apoptotic protease-activation factor-1), dATP, cytochrome c, and procaspase-9, which results in activation of caspase-9 and in turn, activating caspase-3 and final fragmentation of DNA.
In cytoplasm, cytochrome c is known to become associated with caspase-9, Apaf-1 and dATP to form the
apoptosome complex (Chinnaiyan, 1999), which in turn activates caspase- 9, -3 and -7.
Interaction of Cyt c with a cytosolic apoptosis protease activating factor, Apaf-1, induces recruitment of procaspase 9 into a high-molecular-weight complex, termed the
apoptosome, which gives rise to activated caspase-9 and -3.
The released cytochrome c binds to, and activates the adaptor protein Apaf-1, which in turn activates caspase-9, leading to the formation of an
apoptosome and subsequent activation of downstream caspases, such as caspase-3 (Wang, 2001).
2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1
apoptosome.
The study, entitled "Variants in Apaf-1 Segregating with Major Depression Promote
Apoptosome Function," is to be published in the scientific journal, Molecular Psychiatry, Vol.
