Necrosis and apoptosis

Generally speaking, cells have two ways to die. One way is by apoptosis, which is a form of programmed cell death.

The second way is by necrosis, which is when cells die due to injury or disease.

Overall, apoptosis occurs much more often than necrosis.

One example is when old skin cells undergo apoptosis, and get replaced by new skin cells.

Another example is in our hands and feet during fetal development.

Initially, human hands and feet look like duck’s feet, with webs of skin connecting the fingers.

But the cells in the webbing undergo apoptosis and that allows us to form individual digits that allow us to pick our nose and play the piano.

In contrast, necrosis occurs less frequently, and an example of that is when a blood vessel that goes to your big toe gets clogged causing ischemia, which is where oxygen and nutrients can’t reach the cells.

As a result, those cells begin to die, turning your big toe a nasty shade of black.

In apoptosis, there are two activating mechanisms - the intrinsic pathway, also called the mitochondrial pathway, and the extrinsic pathway, also called the death receptor pathway.

The intrinsic pathway occurs when a cell is exposed to stress like radiation, hypoxia, or low oxygen, a high intracellular concentration of calcium ions, or oxidative stress, which is where reactive molecules with unpaired electrons called free radicals steal electrons from nearby molecules.

These stressors cause two intracellular proteins, Bax and Bak, to move from the cytosol to the mitochondria.

Once in the mitochondria, Bax and Bak pierce the outer mitochondrial membrane making it porous and leaky.

This allows two additional proteins, called SMACS and cytochrome C, to spill into the cytosol.

SMACS binds to proteins that normally inhibit apoptosis and deactivates them.

Meanwhile, cytochrome C binds to both ATP - the main form of intracellular energy - as well an enzyme called Apaf-1.

Together, cytochrome C and Apaf-1 combine to form a large protein complex called an apoptosome.

The Apaf-1 portion of the apoptosome then cleaves an enzyme called pro-caspase 9 into its active form, caspase-9.

Caspase 9 then goes on to activate caspase-3, and caspase-3 goes on to activate other caspases - like a chain event.

Eventually this caspase cascade leads a cell to commit apoptosis.

That’s because these caspases cleave the proteins that make up the cell’s nucleus, organelles, and cytoskeleton - a bit like a ninja sabotaging a bridge by removing its nuts and bolts.

This destroys the cytoskeleton, as well as the proteins that anchor the cytoskeleton to the cell membrane.