Apoptogenic factors

Importantly, apoptogenic factors released from mitochondria after GD3 treatment are able to induce DNA fragmentation in isolated nuclei in a cell-... 

The exact manner of how proapoptotic proteins induce the release of apoptogenic factors from the mitochondrial intermembrane space into the cytoplasm and how antiapoptotic proteins prevent it remains obscure. 

Following the outer mitochondrial membrane permeabilization, the apoptogenic factors are released into the cytoplasm. Among them, cytochrome c has an important role in caspase activation, because it is the cofactor for assembling a large caspase 9 activating complex in the cytoplasm, called apoptosome. Along with cytochrome c, the Apaf-1 protein and dATP or ATP are required to form this complex in the cytoplasm (Hill et al., 2003). 

Besides cytochrome c and procaspase 9, other important apoptogenic factors are also released from the mitochondria, such as SMAC/DIABLO, Omi/HrtA2, AIF, and endonuclease G. The function of SMAC/DIABLO and Omi/HrtA2 is to activate caspase by suppressing the caspase inhibitory activity of IAP (Du et al., 2000 Verhagen et al., 2000). The protein... 

The third mechanism is Ca2+-dependent and also involves the intrinsic mitochondrial pathway. Some apoptotic stimuli induce Ca2+ release from the ER, and this process may be regulated by the Bcl-2 family members that reside in this organelle (Szegezdi et al., 2003). Bax and Bak seem to induce Ca2+ release, while antiapoptotic members, such as Bcl-2, seem to reduce this process. Ca2+ ions released from the ER eventually accumulate in mitochondria, which induces permeabilization of the outer mitochondrial membrane through PTP formation. Release of apoptogenic factors... 

Fulda S, Scaffidi C, Susin SA, Krammer PH, Kroemer G, Peter ME, Debatin KM (1998) Activation of mitochondria and release of mitochondrial apoptogenic factors by betulinic acid. J Biol Chem 273 33942-33948... 

Cytochrome C Apoptogenic factor Cellular location A within mitochondra and B when leaks outside. 

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