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All the ways your cells can die

Some cells put on quite a spectacle as they die, exploding in a dramatic burst. Others keep it tidy, quietly packing it in. And while it might seem like overkill for a body to have so many routes to do away with cells, the variety is crucial for the larger organism’s well-being.

The paw of a mouse embryo is paddle-shaped until a type of cell death called apoptosis occurs between the digits to form toes. (Courtesy of Paul Martin)

 

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Until recent decades, scientists thought that cells all died in a haphazard fashion, which they called necrosis. But the great diversity in paths cell death can take has gradually become apparent.

A quick look at what’s been learned so far:

Necrosis: If no known molecular routine switches on to cause the cell’s destruction, it’s typically termed death by necrosis. This is the spontaneous type of death that occurs with a cut to the skin, or from an injury or frostbite.

Apoptosis: This was the first actively regulated route to cell death discovered. In other words, scientists realized the death process some cells follow is an established course controlled by specific molecules. Apoptosis plays an important role in embryo development, it rids the body of cells no longer needed, and it acts as a defense mechanism against diseases such as cancer.

Necroptosis: A cell undergoing necroptosis is not afraid to show it. In fact, a cell undergoing necroptosis as a result of an infection, for instance, erupts and scatters special molecules that alert neighboring cells to the threat. The process is carefully orchestrated by a string of molecules until finally an “executioner” protein drills through the cell’s interior and into the open, causing the cell to rupture and die.

Pyroptosis: Like necroptosis, pyroptosis employs the detonate-and-alert-others-to-danger approach. The process occurs primarily in immune cells and is thought to be key for defending against microbes.

NETosis: Immune cells called neutrophils engage in NETosis to deploy little netlike structures, called neutrophil extracellular traps, to capture microbes that pose a threat to the body. However, the neutrophils themselves sometimes die in the process.

Ferroptosis: As “ferro” suggests, ferroptosis is iron dependent and occurs when the cell is deprived of a particular protein building block called cysteine. Cysteine is needed to make glutathione, a molecule that helps rid the cell of reactive oxygen species that are damaging. Without cysteine, the cell succumbs.

Hanae Armitage is a science writer for the medical school's Office of Communication & Public Affairs. Email her at harmitag@stanford.edu.

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