Imagine waking up one day to a constant racket. You walk out of your house and see that your neighbour鈥檚 townhouse is being deconstructed. A crew is disassembling that house item by item, some of which will be reused somewhere else. You think to yourself, 鈥淎t least they didn鈥檛 use a wrecking ball or my own house might not have been spared.鈥�
Every day, 鈥攖he cells that make up our brain, our heart, our skin鈥攄ie in a very similar process of deconstruction.
It鈥檚 called apoptosis, and it is proof that life is not possible without some form of death.
To pop or not to pop
If you ever find yourself at a cell biology conference and want to sprinkle a little chaos, Joker-style, you could simply ask people how they pronounce the word 鈥渁poptosis鈥� and tell them that they are wrong. There were debates about this . People took positions. The word, by the way, means falling off, and the Greeks apparently used it to describe the falling off of autumnal leaves from trees and of petals from flowers.
When it was to describe a poorly recognized way for cells to die, the authors proposed one pronunciation: ah-puh-TOE-sis. This was in keeping with how the word 鈥減tosis,鈥� meaning the drooping of the upper eyelid, is pronounced in English: the 鈥減鈥� disappears, like in 鈥減sychology.鈥�
Others argued that the 鈥減鈥� should stay, as in 鈥淗umpty Dumpty鈥� and 鈥渉elicopter,鈥� and that it should be pronounced 鈥渁h-pop-TOE-sis鈥� (some even say 鈥渁y-pop-TOE-sis鈥�). There鈥檚 definitely a nice pop to that sound, and it鈥檚 the one I humbly prefer.
Depending on where you grow up in the scientific world and who your teachers are, you go one way or the other on this peculiar word, much like your take on 鈥渧ase鈥� and 鈥渃aramel.鈥�
Beyond these linguistic quarrels, the phenomenon of apoptosis is fascinating. You see, our body generates billions of new cells each day. If the same number of cells did not die, we would turn into a giant, misshapen mass of cells. If that reminds you of cancer, bingo! Cancer is the uncontrolled growth of cells that create tumours. Apoptosis is an important culling tool in the armoury.
It's also the reason why most of us don鈥檛 have webbed toes and fingers. The cells forming this web between our digits typically die off because of apoptosis as we鈥檙e growing in the womb. Apoptosis helps sculpt our body.
There are many ways for our cells to die. Some, like apoptosis, are much less messy than others. The analogy of a house is quite useful.
Extreme Makeover: Cell Edition
Picture a street full of townhouses. Each house is a cell inside our body. One of them has been marked for demolition. There are different ways of achieving this goal.
Necrosis may be the most fun, but it leaves a scar. It鈥檚 like swinging a big wrecking ball at the townhouse. Sure, the house gets demolished, but its neighbours might get hit by falling debris. Necrosis is cell death with collateral damage. It is usually triggered by an injury. The cell swells and everything it contains spills out, causing inflammation in its neighbourhood. It鈥檚 chaotic.
Apoptosis is . It revolves around the activation of a cascade of proteins known as caspases. Much like deconstruction workers being asked to take a house apart, caspases get turned on and work from inside the cell. The DNA gets broken down into short fragments, as do the various organelles of the cell, which could be compared to a house鈥檚 furniture and appliances. The cell shrinks and develops little bubbles at its surface. These bubbles contain the broken-down material of the cell, which can safely leave the cell behind and get eaten up by travelling recycling bins and will make their basic building blocks available to newer cells.
Some have compared apoptosis to a controlled demolition, but I don鈥檛 believe the analogy is correct. Controlled demolition is still messy. A better fit would be another type of cell death, one that was first observed in 2001. It鈥檚 called pyroptosis. It is similar to apoptosis, in that it relies on caspases to break the cell down, but unlike apoptosis, it releases inflammatory molecules into the surrounding environment. There goes the neighbourhood.
Another gruesome cellular death is known as autophagy, meaning 鈥渢o eat itself.鈥� Imagine a house that gets devoured and digested from the inside out by termites. Cells contain little bodies known as lysosomes, full of molecular scissors called enzymes. If a cell isn鈥檛 getting the nutrients it needs to thrive, for example, autophagy can be triggered. The cell eats itself.
There are other ways for cells to die (like entosis, in which one cell engulfs its neighbour), but apoptosis, the careful deconstruction of a cell, remains perhaps one of the most studied. Its role in cancer is indisputable. One of the initiators of apoptosis is a gene called p53, colloquially known as the guardian of the genome, and it is mutated in . If cancer cells aren鈥檛 stopped by apoptosis, they are free to multiply.
A failure in apoptosis has also been tied to autoimmune conditions, in which a person鈥檚 immune system starts attacking healthy parts of the body. Cells of the immune system should not target the self, but errors arise. Apoptosis is supposed to deconstruct these cells; when the process flops, these cells are free to cause damage.
Gaining a clearer understanding of the players in the apoptotic pathway鈥攖he workers recruited to deconstruct houses, essentially鈥攃an lead to interesting therapies. Experimental drugs have been tested and continue to be tested that can either interfere with or trigger apoptosis in order to treat diseases like blood cancers.
The remarkable thing about apoptosis is how predictable it is in biological development. In fact, this reliability was what drew the attention of researchers who would go on to win . Their work was done on a worm known as C. elegans, commonly used in the laboratory. Every worm, like every human, begins its development at conception as a single cell. The adult worm has a fixed number of cells. The scientists who would go on to win the Nobel Prize noticed that during development, the worm would lose 131 cells. Not 130. Not 132. Exactly 131 cells. These cells would die over the course of development through apoptosis. It was thus not an accident; apoptosis was a form of programmed cell death. They identified the genes that were involved in this process and found their homologues in humans.
Houses are torn down to make way for newer structures. Inside our body, billions of little deaths take place every day in order for life to endure.
Take-home message:
- Apoptosis is a type of cell death in which a cell is broken down into small fragments that can be recycled.
- It is different from necrosis, in which a cell leaks out its content, triggering inflammation in the surrounding area.
