Of the three major categories of cell death, apoptosis is what we traditionally refer to when we discuss “programmed cell death,” and it is comparatively the best understood. Cells can receive apoptotic death signals from both cell-extrinsic and cell-intrinsic factors.
External stimuli that can induce apoptosis include 1) infection and 2) death receptor activation. Cells have receptors to detect foreign invaders in the event of an infection. These receptors mediate an inflammatory response, which can help immune cells recognize and help kill the infected cell. Death receptors on the outside of the cell can recognize death signals as well. These signals may be released by dying cells, such as in a tumor.
When things go awry within the cell (e.g. DNA damage or endoplasmic reticulum, or ER, stress), cells undergo 3) mitochondrial apoptosis. As a site of adenosine triphosphate (ATP) production, the mitochondria are organelles that we typically associate with cellular energy. In response to apoptotic stimuli, however, they become permeable, release cytochrome c, and activate a cascade of enzymes called caspases that ultimately cleave up DNA and mediate cell execution.
