mTOR signaling in protein homeostasis: less is more?

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.