The Basics of Apoptosis

Apoptosis is the cellular equivalent of a “self-destruct button.” It’s a controlled process that rids the body of cells that are no longer needed. Like cell division, apoptosis is critical for healthy tissue growth and development.

Apoptosis happens when a cell is sick, injured, or in need of rearranging itself to make way for newer cells. It’s also important for maintaining homeostasis in the body.

It can be normal or it can lead to cancer. Apoptosis is the process by which cells die in a controlled manner so that the resulting cell death does not damage other tissues or trigger immune responses.

During apoptosis, cells undergo a series of morphological changes that are accompanied by release of cellular proteases and disintegration of chromatin and membranes. Several lipids, including phosphatidylserine, that are normally located in the plasma membrane change their location and appear in the cytoplasm as well. In addition, blebbing of the plasma membrane is observed, and the nucleus and cytoplasm fragment into numerous apoptotic bodies.

Apoptotic cells are recognizable by a brightly labeled protein, annexin V. The fluorescent protein is found in the cytosolic leaflet of the plasma membrane; during apoptosis, annexin V flips to the exoplasmic leaflet and is seen in the outer membrane (Figure 1).

There are two main pathways to apoptosis: the extrinsic pathway, which occurs by way of external stimuli such as ligand binding at death receptors on the cell surface or a cell injury, and the intrinsic pathway, which is triggered by internal signals within the cell that cause caspase activation.

The intrinsic pathway involves a sequence of steps that begin with a molecule called BID that is kept inactive until it’s cleaved by activated caspases. It then moves to the mitochondria and is transformed into a molecule called tBID, which then activates molecules BAX and BAK.

After BAX and BAK are activated, they move to the nucleus and induce a series of events. One of these is the formation of a complex, highly active molecule called ROCK I that causes apoptosis through an enzyme-mediated process that leads to a caspase cascade and cellular blebbing.

Another step is cytoskeletal collapse, which causes the cell to shrink and send out distress signals. These are recognized by vacuum cleaner-like macrophages that engulf the apoptotic body and digest it to remove its contents.

In addition to removing unwanted cells, apoptosis may have other important functions as well. For example, it can help sculpt the human hand and other body parts by eliminating cells that are not necessary for development.

It can also help prevent disease by reducing the number of dead, nonfunctional or malignant cells in an organism. In fact, it can be responsible for preventing certain conditions that have a high rate of recurrence and are associated with poor health outcomes, such as heart diseases and brain tumors.

Apoptosis is also a key component of the autophagy mechanism, which helps clean up accumulated toxins and waste products in the body. In addition, apoptosis can help protect against inflammatory diseases by preventing the release of immune-stimulatory proteins that would otherwise be present in the extracellular space.