Intrinsic Apoptosis Pathway

1. Intrinsic Apoptosis Pathway Intracellular cues, such as damage to the cell's DNA, drive apoptosis primarily through the intrinsic pathway. The intrinsic apoptosis pathway, which involves conserved signaling proteins, is physically associated with mitochondria, and in vertebrates is sensitive to mitochondrial oxidative stress. The pathway is influenced by members of the Bcl family bound to the mitochondrial membrane, including Bax and Bcl-2 gene, which act as pro- or anti-apoptotic regulatory proteins, respectively. The intrinsic apoptosis pathway is initiated by, for example, chemotherapy and/or radiotherapy. It is activated by a range of exogenous and endogenous stimuli, such as DNA damage, ischemia, and oxidative stress. Moreover, it plays an important function in development and in the elimination of damaged cells. In the intrinsic pathway, the functional consequence of pro-apoptotic signaling is mitochondrial membrane perturbation and release of cytochrome c in the cytoplasm, where it forms a complex or apoptosome with apoptotic protease activating factor 1 (APAF1) and the inactive form of caspase-9. This complex hydrolyzes adenosine triphosphate to cleave and activate caspase-9. The initiator caspase-9 then cleaves and activates the executioner caspases-3/6/7, resulting in cell apoptosis. It's totally different from the extracellular signals, which are usually generated by cytotoxic cells of the immune system and trigger apoptosis mainly through the extrinsic pathway. Find more: https://www.creative-diagnostics.com/intrinsic-apoptosis-pathway.htm