Cells die two ways. If you stab yourself in the thigh with a pencil, cells of the tissue injured by your sharpened graphite will die via necrosis, or accidental cell death. Necrosis is messy. Cells swell and burst, spewing their contents onto neighboring cells. This is undesirable—what’s inside of cells is inside of cells for a reason. When allowed to run around willy-nilly in the space outside of cells, certain molecules cause an inflammatory response. Inflammation is why the hole left by your pencil will hurt, but also allows this wound to heal.
There is, however, a better and yummier-sounding way to die. Although the name recalls Pop-Tarts, the sugary, colorful breakfast rectangles of youth, apoptosis is programmed cell death. It’s much neater than necrosis. Instead of exploding, a cell undergoing apoptosis tidily shrinks and breaks into fragments, allowing neighboring cells to eat the leftover bits of its corpse. Its contents are never released, so there is no inflammatory response.
These are basically the same thing, right? (Photo credit: http://www.seriouseats.com and http://www.medchemexpress.com)
Apoptosis, also known as cell suicide, is necessary. It occurs in adults on a regular basis to keep our total number of cells in check: as cells multiply, other cells kill themselves to keep our cell count balanced. Otherwise, we’d be riddled with odd growths. But apoptosis really shines during development. Though we think of development as a generative process in which we transform from a wee-little ball of cells into a fully formed fetus, it’s also a time during which perfectly healthy cells are destroyed. Waves of cell suicide grant us our digits, removing webbing from between fingers and toes. Apoptosis deletes our embryonic tails and creates our inner ear spaces. More than half of the neurons (nerve cells) in our nervous systems died via apoptosis during development, to refine and strengthen connections between surviving neurons.
How does a cell neatly self-destruct? It begins when specific signals activate, or “turn on,” an adaptor protein. These signals vary depending on the situation. They may come from outside or inside of a doomed cell. Turning on an adaptor protein causes a bunch of other proteins to clump together, the adaptor proteins and the newly recruited proteins interlocking like the pieces of a puzzle. The newly recruited proteins are known as procaspases. Procaspases are inactive, “turned-off,” proteins—they spend their days twiddling their thumbs, waiting for the call of an activated adaptor protein. Only when an adaptor protein collects them en masse are the procaspases activated. An activated procaspase is called a caspase. Caspases are like hyperactive molecular scissors, all revved up and ready to cut stuff. The first wave of caspases (activated by the adaptor protein) cut other procaspases to activate them; the second wave of caspases (activated by the first wave) then degrades the structural integrity of a cell, allowing it to condense and fragment into apoptotic bodies. Surrounding cells swallow apoptotic bodies, completing a cell’s suicide.
This self-amplifying caspase cascade is comprised of proteins coded for in a cell’s DNA. This is why apoptosis is considered “programmed” cell death: the instructions to build proteins that can kill a cell are written in its own blueprints. They exist, as procaspases, at all times—lying in wait for the right set of signals.