An Introduction to Apoptosis

In normal tissues there is a balance between the generation of new cells via cell division and the loss of cells via cell death. Old cells become damaged over time and are eliminated.  This is an essential form of renewal.  Examples include shedding of skin cells and the replacement of the cells lining our digestive tract.  Like cell division, cell death is also tightly controlled.   Cells frequently die by a process termed programmed cell death or apoptosis. ⁽¹⁾ Apoptosis is the cellular equivalent of a “self destruct” button.

Apoptosis is a very orderly process during which the genome of the cell is broken down, the cell is fragmented into smaller pieces and the debris is consumed by nearby cells (phagocytes) that clean up the cell fragments. Besides getting rid of damaged, potentially dangerous cells, apoptosis is crucial for embryological development and neurologic pruning. The term “apoptosis” comes from the Greek words apo (from) and ptosis (falling) and it was used to describe leaves falling from a tree. ⁽²⁾

There are two distinct phases in apoptosis, the initiation phase and the execution phase. The initiation phase involves many different proteins and it is quite complex. It is started by various “stresses” from either outside the cell (extracellular) or inside the cell (intracellular). ⁽³⁾ Some examples of extracellular signals that trigger apoptosis include loss of growth factors, low oxygen levels (hypoxia), and radiation. Intracellular signals include DNA damage, the damage caused by chemotherapydrugs, telomere malfunction, and infection with viruses. The initiation phase triggers the execution phase.  The execution phase involves the activation of specialized enzymes (caspases and others) that directly result in cell death. ⁽³⁾

1. Vo TT, Letai A. BH3-only proteins and their effects on cancer. Adv Exp Med Biol. 2010;687:49-63. [PUBMED]
2. Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011 Sep 26;30:87 [PUBMED]
3. Bender T, Martinou JC. Where killers meet–permeabilization of the outer mitochondrial membrane during apoptosis. Cold Spring Harb Perspect Biol. 2013 Jan 1;5(1):a011106 [PUBMED]