Topic: Apoptosis

A cell in the eye of a fruit fly undergoes apoptosis. Several Rockefeller labs study the mechanisms that cells use to trigger their own deaths.

Many billions of cells in the human body self-destruct every day in a process of programmed cell death called apoptosis. A critical mechanism by which aging and sick cells make way for new healthy ones, apoptosis also helps organisms get rid of potentially dangerous cells, such as those that are virally infected or precancerous. Apoptosis is also crucial in early development — when some cells, such as those that would otherwise form webbing between human fingers and toes, are programmed to die — and in the tuning and trimming of the nervous system.

The cellular machinery that supports this capability for self-destruction is ever present, and to stay alive cells require the activity of teams of “inhibitor” molecules that prevent apoptosis from occurring prematurely. Researchers have found that it is possible to block the activity of these “inhibition of apoptosis” (IAP) proteins, thereby triggering cell death. Studying apoptosis in fruit flies, Rockefeller’s Hermann Steller identified a protein named Reaper in 1994 that works with several other molecules, including Grim and Hid, to interfere with the protective activity of IAPs, thereby taking the brakes off of apoptosis. Related molecules are found in humans, and scientists are working to develop small-molecule IAP antagonists that may be able to fight tumors.

Several additional Rockefeller scientists are also working to better understand apoptosis. Sanford Simon has used single cell microscopy to reveal an unsuspected order to what was thought to be the random timing or sudden collapse of cells undergoing apoptosis. Shai Shaham has found a new type of programmed cell death that doesn’t rely on the traditional class of executioner molecules, called caspases.

A clearer picture of the proteins and pathways involved in apoptosis could suggest means of triggering death in targeted populations of cells, such as tumors, and preventing it in others, such as healthy neurons that store memories.