Apoptosis, necroptosis, and pyroptosis, oh my —
Some go gently into the night. Others die less prettily.
Enlarge / 3D rendering of an NK Cell destroying a cancer cell.
Billions of cells die in your body every day. Some go out with a bang, others with a whimper.
They can die by accident if they’re injured or infected. Alternatively, should they outlive their natural lifespan or start to fail, they can carefully arrange for a desirable demise, with their remains neatly tidied away.
Originally, scientists thought those were the only two ways an animal cell could die, by accident or by that neat-and-tidy version. But over the past couple of decades, researchers have racked up many more novel cellular death scenarios, some specific to certain cell types or situations. Understanding this panoply of death modes could help scientists save good cells and kill bad ones, leading to treatments for infections, autoimmune diseases, and cancer.
“There’s lots and lots of different flavors here,” says Michael Overholtzer, a cell biologist at Memorial Sloan Kettering Cancer Center in New York. He estimates that there are now more than 20 different names to describe cell death varieties.
Here, Knowable Magazine profiles a handful of classic and new modes by which cells kick the bucket.
Unplanned cell death: Necrosis
Lots of bad things can happen to cells: They get injured or burned, poisoned or starved of oxygen, infected by microbes or otherwise diseased. When a cell dies by accident, it’s called necrosis.
There are several necrosis types, none of them pretty: In the case of gangrene, when cells are starved for blood, cells rot away. In other instances, dying cells liquefy, sometimes turning into yellow goop. Lung cells damaged by tuberculosis turn smushy and white — the technical name for this type, “caseous” necrosis, literally means “cheese-like.”
Any form of death other than necrosis is considered “programmed,” meaning it’s carried out intentionally by the cell because it’s damaged or has outlived its usefulness.
A good, clean death: Apoptosis
The two main categories of programmed cell death are “silent and violent,” says Thirumala-Devi Kanneganti, an immunologist at St. Jude Children’s Research Hospital in Memphis, Tennessee. Apoptosis, first named in 1972, is the original silent type: It’s a neat, clean form of cell death that doesn’t wake the immune system.
That’s handy when cells are damaged or have served out their purpose. Apoptosis allows tadpoles to discard tail cells when they become frogs, for example, or human embryos to dispose of the webbing between developing fingers.
The cell shrinks and detaches from its neighbors. Genetic material in the nucleus breaks into pieces that scrunch together, and the nucleus itself fragments. The membrane bubbles and blisters, and the cell disintegrates. Other cells gobble up the bits, keeping the tissue tidy.
Enlarge / In necrosis, a cell dies by accident, releasing its contents and drawing immune cells to the site of damage by creating inflammation. In apoptosis, the cell collapses in on itself and the bits are cleared away without causing damaging inflammation.
