In several of our posts, we’ve touched on apoptosis. This is often called “programmed cell death” to distinguish it from necrosis. If apoptosis is orderly suicide, necrosis is a violent and unnatural death in which, unlike apoptosis, the cell doesn’t intend to die.
Apoptosis might seem like an odd idea, but it is simply a realisation of the need to occasionally delete one’s own cells. This requirement crops up again and again:
- To delete excess tissue in embryogenesis (e.g. creating a gut lumen out of a solid tube).
- To kill cells infected by a virus or other microorganism.
- To kill neoplastic cells.
- To kill cells that are irreparably damaged.
- To kill self-reactive lymphocytes (thereby ensuring immune tolerance).
In these cases, the body prefers to kill the cells by the orderly process of apoptosis, which doesn’t incite a costly and potentially damaging immunological reaction, rather than the messy process of necrosis, which does. (It’ll resort to the latter if it has to, though.)
There are three main conceptual stages to apoptosis.
1. Signal integration
Our cells are must constantly decide between two conflicting orders: to apoptose, or not to apoptose, as Bill might have said. Of course, usually the decision is the latter, but if the “apoptose now!” signals are particularly strong, the relevant cells are forced to change their minds. Things can also work in the opposite direction: if a cell has strong enough “don’t apoptose, you idiot!” signals it can survive a bombardment of signals that would cause any normal cell to apoptose. This is one trick that many cancers use to avoid this fate.
The main pro-apoptosis signals are fourfold:
· Mitochondrial damage
· Severe DNA damage
· Severe cell membrane damage
· Direct signal transduction
The latter means that apoptosis can also be brought about when specific substances bind to specific cellular receptors. One that crops up a lot in immunology is the Fas-Fas ligand interaction. For instance, an activated cytotoxic T cell expresses the Fas ligand, allowing this ligand to bind to the target cell’s Fas receptor. This interaction signals the target cell to commence apoptosis. Similarly, if enough TNF binds to receptors on a particular cell, apoptosis may also be induced.
2. Executioner pathway activation
If the “apoptose now!” signals preponderate, the cell becomes committed to apoptosis. The chief set of actors here appear to be the caspases, specific proteases that become activated as part of the evocatively-named “executioner pathway”.
The caspases set about dismantling the cell. Cell specialisations (like cilia) and intercellular junctions are amongst the first to go, and the cell volume starts shrinking. The chromatin condenses, and both the chromosomes and the nucleus itself are cleaved into fragments. There is also a change in the cell membrane’s phospholipid content (it becomes high in phosphaditylserine, for what it’s worth). Interestingly, unlike in necrosis, the cell’s organelles remain unmolested. Eventually the cell is fragmented into several small apoptotic bodies.
The phosphaditylserine of the apoptotic bodies acts as a marker for phagocytes, so that they are soon engulfed and more thoroughly degraded.
The system is really quite efficient – the whole process can be over in minutes, with virtually no disruption to surrounding tissues since apoptosis doesn’t elicit a proper inflammatory response.
This is pretty much the level I’m happy with knowing, personally. The full story, in all its profligate detail, is utterly pointless unless that’s your area of research. If you don’t want to take my word for it, click here to see the entire pathway, and you’ll see what I mean. Go on, I dare you…