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Hello my Professor has been teaching about apoptosis and sometimes makes the distinction between extrinsic and intrinsic. I am not sure if I know for sure what this means. Does this just refer to intrinsic is a cell doing itself while extrinsic refers to Fas ligand? Thanks.

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In both pathways 'the cell does itself' the difference is in the reason.

In short: Intrinsic apoptosis is a response to 'internal damage' eg. damaged DNA, chromosom rearrangement, hang ups in division, hypoxia, etc. that the cell senses itself and 'decides to commit suicide'. This is done by the mitochondrial pathway - release of cytochrome C from the mitochondria activates the caspase cascade that results in programmed cell death. This is like "I'm too damaged, I must die".

In the extrinsic pathway as you have mentioned is indeed related to the FAS ligand (and Fas/FasL being the main pathway for apoptosis), but that is not the only external signal as TNF (also known as TNA-alpha) binding to TNF-R1 (tumor necrosis factor receptor 1) may also lead to apoptosis. These pathways are usually activated by the immune system for example in cellular immune response. This is like "You're abnormal / dangerous / infected, you must die".

Both pathways activates the caspase cascade at some point that results in apoptosis. Either way the actual process of apoptosis is carried out by the cell itself in a programmed, regulated manner.

Source: http://en.wikipedia.org/wiki/Apoptosis This papaer offers a great review on the topic, including both pathways: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117903/

I'd like to quote few important parts to support my answer:

The extrinsic, intrinsic, and granzyme B pathways converge on the same terminal, or execution pathway. This pathway is initiated by the cleavage of caspase-3 and results in DNA fragmentation, degradation of cytoskeletal and nuclear proteins, cross-linking of proteins, formation of apoptotic bodies, expression of ligands for phagocytic cell receptors and finally uptake by phagocytic cells.

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The extrinsic signaling pathways that initiate apoptosis involve transmembrane receptor-mediated interactions. These involve death receptors that are members of the tumor necrosis factor (TNF) receptor gene superfamily

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The intrinsic signaling pathways that initiate apoptosis involve a diverse array of non-receptor-mediated stimuli that produce intracellular signals that act directly on targets within the cell and are mitochondrial-initiated events.

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  • $\begingroup$ Note that the TNFR superfamily is quite large - in this Cell paper from 2001 (sorry, not open access), it lists 26 known receptors binding to at least 18 known ligands. $\endgroup$
    – MattDMo
    Apr 23, 2015 at 14:52
  • $\begingroup$ Absolutely true, I've added that TNF-alpha bindig to the TNF-R1 may lead to apoptosis. The quote is there to justify the general idea that some members of the TNF superfamily play role in apoptosis. Thank you for your remark! $\endgroup$ Apr 23, 2015 at 15:28
  • $\begingroup$ I would actually change the example to Fas/FasL, as that interaction almost always leads to apoptosis. While TNFα is pro-apoptotic in some circumstances, there are many cases where it isn't, as it is mostly regarded as a pro-inflammatory cytokine, helping to activate cells responding to infection. However, when cytotoxic cells express FasL and bind to a target cell expressing Fas (the receptor), that (almost) always leads directly to the induction of apoptosis. I just think it would be a more clear-cut example. Your choice, though :) $\endgroup$
    – MattDMo
    Apr 23, 2015 at 17:05
  • $\begingroup$ I wnated to point out that not only Fas/FasL can induce apoptosis, but I'll emphasize that Fas/FasL is the main component. $\endgroup$ Apr 23, 2015 at 17:09

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