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Mitochondrial Pathway Of Mitochondrial And Mitochondrial Permeability Transition

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1.2.2. Mitochondrial pathway
The mitochondrial pathway, also called intrinsic pathway, because it is initiated from inside the cell. Various stimuli such as growth factors withdrawal, DNA-damage, hypoxia, and oxidative stress can induce apoptosis through this cascade. These insults cause increasing permeability of the outer mitochondrial membrane and opening of the mitochondrial permeability transition (MPT) pore which is controlled by members of the Bcl-2 family proteins. This large family of proteins is defined by the presence of conserved Bcl-2 homology domains (BH1 to BH4). Up to 30 Bcl-2 family genes have been identified in mammals, which have either pro-apoptotic or anti-apoptotic functions. Some of the anti-apoptotic members include Bcl-2 itself, Bcl-XL, Bcl-w, BAG and Mcl-1 which possess all domains of BH1 to BH4. The pro-apoptotic family proteins can be divided into two subgroups: consists of Bak, Bax, and Bok with possess BH1 to BH3 domains, and Bad, Bid, Bik, BNIP3, Bim, Bmf, Blk, Hrk, Noxa, Puma, and Spike) that only possesses BH3 domain [Cory, 2002; Mund, 2003]. It is believe that BH3-only proteins interfere with the fine-tuned balance of homo- or hetero-oligomerization between pro-apoptotic multidomains (eg., Bax/Bak) and anti-apoptotic members (eg., Bcl-2/Bcl-XL) (Figure 3). In general, oligomers of Bak, Bax, and Bok induce PMT, either by forming channels by themselves or by interacting with components of the PMT [Antonsson, 2000]. Bad can also heterodimerize

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