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Review
. 2011 Jun 15;10(12):1940-7.
doi: 10.4161/cc.10.12.15858. Epub 2011 Jun 15.

mTOR signaling in protein homeostasis: less is more?

Crystal S Conn  1 , Shu-Bing Qian
Affiliations
Review

mTOR signaling in protein homeostasis: less is more?

Crystal S Conn et al. Cell Cycle. .

Abstract

A proper balance between synthesis, maturation and degradation of cellular proteins is crucial for cells to maintain physiological functions. The costly process of protein synthesis is tightly coupled to energy status and nutrient levels by the mammalian target of rapamycin (mTOR), whereas the quality of newly synthesized polypeptides is largely maintained by molecular chaperones and the ubiquitin-proteasome system. There is a wealth of evidence indicating close ties between the nutrient signaling pathway and the intracellular stress response. Dysregulation of both systems has been implicated in aging and age-associated pathologies. In this review, we describe molecular mechanisms underlying the connection between mTOR and the chaperone network and discuss the importance of their functional interaction in growth and aging.

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Figures

Figure 1
Figure 1
HSF1-mediated stress response. The conversion between inactive HSF1 monomer and active HSF1 trimer is controlled by chaperone availability in cells. Chaperone availability, on the other hand, is governed by the balance between protein synthesis and folding requirement. Stress conditions, such as heat shock, lead to the accumulation of misfolded proteins, which subsequently triggers the stress response in order to achieve protein homeostasis.
Figure 2
Figure 2
mTOR signaling pathway. mTORC1 and mTORC2 receive distinct upstream signals from both extracellular and intracellular stimuli and have different downstream targets. Notably, interconnection between mTORC1 and mTORC2 occurs at several levels. For example, one of the mTORC2 downstream targets, Akt, serves as an upstream regulator of mTORC1, whereas one important mTORC1 target ribosome acts as an activator of mTORC2. Most of the signaling components are involved in growth and aging, and lots of mutations have been found in human diseases such as cancer. For simplicity, only typical mTOR components are shown. See the main text for details.
Figure 3
Figure 3
The interface between chaperone-mediated stress response and mTOR-mediated nutrient-sensing system serves as a central homeostatic mechanism. Dysregulation of both pathways has been implicated in aging and age-associated diseases.
See this image and copyright information in PMC

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