all right welcome back to our discussion on apoptosis in this particular video I want to distinguish between two kinds of ways of how to initiate so apoptosis can be initiated by an intrinsic way from the inside out and that what pretty much be happening without the need of the initiator caspases that goes right to the executioner's that can cut up the cell and then we have the extrinsic pathways from the outside via receptors that utilize the initiator caspases that i mentioned in the previous lecture all right here we go so this is the intrinsic pathway this is what's happening of or this is how a cell and eukaryotic cell specifically will destroy itself from the inside out if you remember we I said that p53 has that power and I'll come back into the next lecture so I'll tell you exactly how 53 does that p53 can kill the cell and here's how it does it p53 provides the stimulus for either a molecule called backs or back to release cytochrome C from the mitochondrion okay I'll say it again you should recognize cytochrome C as a part of the electron transport chain right so the electric transport chain sits in the mitochondria and cytochrome C is part of that backs and back can go in the mitochondria and release it so cytochrome C has no function in side the cell other than it's a signal in the cytoplasm to undergo a cell suicide so here we go cytochrome C released from the mitochondria using back and back backs and back and these in red right here these cytochrome C molecules will then bind to adapter proteins shown right here means adapter proteins are always present but generally they don't find a binding partner of cytochrome C unless the cell attempts suicide when that happened these are depta proteins self-assemble into this seven starred a seven armed ninja star right here okay this and this is a scaffold that will load the pro cast space is nine in it and cleave and activated okay so we have seven armed adapter molecules right here my and by the way pro caspase-3 and 9 so caspase-3 and nine are always gonna be your your executioner's and eight and ten are your initiator caspases so it takes an execution of caspase loads it in here which then forms what we call the apoptosis you know scientists call things ohms whenever we don't know but what's called it's a complex right so the apoptosis is a complex of adapter proteins right here in instead of yellow the cytochrome c has been released from the mitochondria by back so back in red and the cleaved caspase-9 so if you see cleave caspase-9 that means that cell is in the process of killing itself and it's actually quite vicious like this thing looks dangerous and it's kind of like a saw blade where it goes around in the cell and cats sort of indiscriminately cellular proteins again including the cytoskeleton that sort of has the cell collapse on itself so that's the intrinsic pathway and p53 can make this happen Pipo p3 can say backs and back go release cytochrome c from that from the mitochondria and that's the end of that cell we also can have it you also have an extrinsic pathway that's shown right here extrinsic means as the signal comes from the outside and that usually yes involves cell surface receptors so you probably told you some of my previous lectures but your cell surfaces are truckful with death receptors okay so this one is called fast which stands for fatty acid ligase or fatty acid synthase because that's how it was first identified but all of these d r stands for death receptor TNF R is too many kosis factor receptor so these are all death receptor that that respond to different signals some of them are activated by the immune system some of them are activated by cytokine so this one TNF tumor necrosis factor that is a killing me the cancer cell molecule right here what they have in common is on the inside they have two very same domain from the outside they're buying six different signals but from the inside they have the same domain then the main looks like this it's embedded right here and part of this domain right here is the caspase 8 and 10 the initiator caspases are actually part of the receptor of the inside and if something binds on the outside these will be cut off okay so this this whole domain right here is called the death inducing signaling complex or disk if you will okay so but the point is that the caspases are built in the initiator caspases are building into the intracellular domain of the receptor and upon binding they will be severed and if there's enough of them began this one won't do it you have to have a high enough concentration so they find one another and then actually constitute a a a functioning initiator caspases pair and they will then initiate a execution of caspase cascade that's what's implied right here they cut executional caspases in the execution of caspase take care of the cell and here's the apoptosis here see these little bubbles be blebbing than Alison I love this term that I was referring to earlier when you cut the cytoskeleton that actually props up the the plasma membrane all right so that's that and so again yeah so my fast lagging domain on in the intracellular domain will release the initial or cleave the initiator caspases and so again if we want to see by the way so here's one way of how we we look this if we want to see if a cell dies but it dies from the inside out or the outside in we can actually look whether these initiator caspases have been having cleave right so we can look at the action of these death receptors and few serious initiator caspases it's the extrinsic pathway that is being done all right so with that I'll be right back