A suggested mechanism by which autophagy inhibits apoptosis is the sequestration of mitochondria damaged by the autophagosome, thus preventing the released mitochondrial cytochrome c to form a functional apoptosome
in the cytoplasm (53).
Regulation of the Apaf-1-caspase-9 apoptosome
. J Cell Sci 2010; 123: 3209-3214, doi: 10.1242/ jcs.073643.
The released cytochrome c interacts with apoptotic protease-activating factor 1 and forms an apoptosome
that activates caspase 9, leading to the activation of downstream caspases 3 and 7 and the apoptotic death response [39-42].
Cytochrome c activates procaspase 9, resulting in formation of the apoptosome
Rehm, "A systems biology analysis of apoptosome
formation and apoptosis execution supports allosteric procaspase-9 activation," The Journal of Biological Chemistry, vol.
Briefly, the interaction between HK2 and voltage-dependent anion channel (VDAC1) reduces the release of proapoptotic proteins and prevents cancer cells from undergoing apoptosis ; phosphoglucose isomerase exerts its antiapoptosis effect by suppressing the expression of Apaf-1 and caspase-9 genes, thereby indirectly regulating the formation of the apoptosome
A molecular view on signal transduction by the apoptosome
. Cell Signal 2012; 24: 1420-5.
In general, intrinsic apoptosis is a mitochondrion-centered cell death that is mediated by mitochondrial outer membrane permeabilization, and results in apoptosome
formation, activation of caspase-9, and subsequent activation of effector caspases.
Cytochrome-c interacts with APAF-1 and CASPASE-9 to form the apoptosome
leading to apoptosis (Tanimoto et al., 2005).
Salvesen, "The apoptosome
: signalling platform of cell death," Nature Reviews Molecular Cell Biology, vol.
The Cyt c forms a complex with procaspase-9 and Apaf-1 and stimulates the formation of apoptosome
that further activate caspase-9.
When cytochrome c accumulates in the cytosol, it complexes with procaspase-9 and Apaf-1 to form the "apoptosome
", which in turn activates caspase-3 (Figure 2) .