Pathways for apoptosis induction or inhibition originate from both extrinsic and intrinsic signalling systems.

Extrinsic Activation of Apoptosis:The extrinsic pathway is initiated by ligand binding to cell surface death receptor, and this binding induces the assembly of a death-inducing signlaing complex that facilitates activation of initiator caspase-8.

Extrinsic signalling pathways are initiated by ligand binding to cell-surface receptors (e.g., Fas ligand binding to Fas/Apo1/CD95). Intrinsic signalling involves the activation and oligomerization of proteins (e.g., BAX) that are capable of binding and destablizing mitochondrial membranes. In most cases, both extrinsic and intrinsic apoptosis require the activation of a family of proteases (CASPASES) and culminate in the participation of nucleases and other destructive enzymes that eliminate cells without eliciting inflammation. Both apoptotic pathways converge on the activation of caspase-3 which is the executioner of apoptosis.

• : The extrnsic pathway is mediated by ligation of a death receptor upon its binding to a death-inducing ligand that results in the activation of caspase-8, which activates caspase3. Extrinsic initiation of apoptosis occurs by stimulation of sets of surface receptors (e.g.,  or TNFR) by their cognate ligands. This results in trimerization and docking of proteins containing so-called death domains which in turn activate large amounts of caspase 8, an initiator caspase, followed directly by cleavage of downstream effector caspases in Type I cells. By contrast, Type II cells produce little activate caspase 8 and therefore relay on a mitochondrial amplification step.

The extrinsic pathway can be induced by interactions between  (such as , interferon-gamma and TGF-B) and death receptors, resulting in activation of Casp-8.  : 

Intrinsic Activation of Apoptosis: The intrinsic pathway involves induced permeabilization of the outer mitochondrial membrane, leading to the release of several proapoptotic factors, including cytochrome C and SMAC, that cooperate to faciliate activation of initiator caspase-9, which in turn, leads to activation of effector caspases such as caspase-3.

• : The instrinsic pathway is mediated by agents such as stress stimuli and toxins that cause the release of cytochrome c from mitochondria into the cytoplasms and result in activation of caspase-9 which activates caspase-3. The Intrinsic induction of apoptotis starts within the cell and can occur by direct activation of caspases or a variety of stress-related mechanisms. The intrinsic pathway is triggered in response to a variety of apoptotic stimuli including anticancer agents, oxidative damage, UV irradiation and growth factor withdrawal and is mediated through mitochondria. These stimuli induce the loss of mitochondrial membrane integrity and result in the critical event — release of multiple molecules, including cytochrome c (cyt c), which associates with Apaf-1 and Casp-9 to promote caspase activation.

The release of cytochrome c is largely controlled by members of proteins of the Bcl-2 family, which can act to promote or to inhibit this release. On a molecular level, free cytosolic cytochrome c initiates the formation of a signaling complex (called the apoptosome) that encompasses the molecules Apaf-1 and the proteases caspase-9 and caspase-3. In the formation of this complex, caspase-9 is activated with in turn activates caspase-3. Active caspase-3 then cleaves cellular substrates to bring about the morphological changes of apoptosis such as nuclear condensation.

• granzyme B pathway, where the cytotoxic cell protease granzyme B is delivered to sensitive target cells.

Although apoptosis through death receptors does not appear to require the involvement of mitochondria, several levels of cross-talking exist between these two pathways. For example, the Bcl-2 family plays an important role in this cross-talking by acting on mitochondria. Active capase-8, the downstream effector caspase of the extrinsic pathway can cleave the cytosolic Bid into the BH3-only domain-containing, proapoptotic, truncated tBid fragment which can translocate into mitochondria, where it binds to its mitochondrial proapoptotic partner Bax or Bak to trigger the release of cyt c into the cytosol. In certain cell lines, overexpression of Bcl-2/Bcl-xl prevents the efflux of cyt c from the mitochondria, and can prevent cell death receptor-induced apoptosis.