Regulation of Autophagy by the Target of Rapamycin (Tor) Proteins
Administration of the small macrolide antibiotic rapamycin to eukaryotic cells results in
physiological responses that mimic nutrient starvation, and in many ways resembles
nitrogen starvation. The target for rapamycin action in these cells is a family of conserved
kinases known as TOR (target of rapamycin). Tor kinases are essential for the normal
function of eukaryotic cells and participate in the integration and control of nutrient-sensing
signals. Inhibition of Tor by rapamycin triggers a variety of molecular responses. These include
global changes in gene expression, which are mediated by effects on both transcription and
translation, as well as direct effects on other cellular processes. Within this context, inhibition
of TOR has a number of effects on membrane trafficking, including the induction of autophagy.
This chapter represents a compendium of our current state of knowledge on the role of
TOR family proteins, their architecture and molecular interactions, as well as the mechanisms
by which inhibition of TOR leads to various cellular responses. This general perspective is
aimed at understanding the relative role of the induction of autophagy within the broader
response of cells to rapamycin and starvation.