Twenty-five years of mTOR: Uncovering the link from nutrients to growth.

Proc Natl Acad Sci U S A
Authors
Keywords
Abstract

In my PNAS Inaugural Article, I describe the development of the mTOR field, starting with efforts to understand the mechanism of action of the drug rapamycin, which ∼25 y ago led to the discovery of the mTOR protein kinase. I focus on insights that we have contributed and on work that has been particularly influential to me, as well as provide some personal reflections and stories. We now appreciate that, as part of two distinct complexes, mTORC1 and mTORC2, mTOR is the major regulator of growth (mass accumulation) in animals and is the key link between the availability of nutrients in the environment and the control of most anabolic and catabolic processes. Nutrients signal to mTORC1 through the lysosome-associated Rag GTPases and their many regulators and associated cytosolic and lysosomal nutrient sensors. mTOR signaling is deregulated in common diseases, like cancer and epilepsy, and mTORC1 is a well-validated modulator of aging in multiple model organisms. There is significant excitement around using mTORC1 inhibitors to treat cancer and neurological disease and, potentially, to improve healthspan and lifespan.

Year of Publication
2017
Journal
Proc Natl Acad Sci U S A
Volume
114
Issue
45
Pages
11818-11825
Date Published
2017 11 07
ISSN
1091-6490
DOI
10.1073/pnas.1716173114
PubMed ID
29078414
PubMed Central ID
PMC5692607
Links
Grant list
HHMI / Howard Hughes Medical Institute / United States