mTOR: a pharmacologic target for autophagy regulation
Young Chul Kim, Kun-Liang Guan
Young Chul Kim, Kun-Liang Guan
Published January 2, 2015
Citation Information: J Clin Invest. 2015;125(1):25-32. https://doi.org/10.1172/JCI73939.
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Review

mTOR: a pharmacologic target for autophagy regulation

Abstract

mTOR, a serine/threonine kinase, is a master regulator of cellular metabolism. mTOR regulates cell growth and proliferation in response to a wide range of cues, and its signaling pathway is deregulated in many human diseases. mTOR also plays a crucial role in regulating autophagy. This Review provides an overview of the mTOR signaling pathway, the mechanisms of mTOR in autophagy regulation, and the clinical implications of mTOR inhibitors in disease treatment.

Authors

Young Chul Kim, Kun-Liang Guan

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Figure 2

Regulation of autophagy by mTORC1.

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Regulation of autophagy by mTORC1. Activation of mTORC1 by nutrients and...
Activation of mTORC1 by nutrients and growth factors leads to inhibition of autophagy through the phosphorylation of multiple autophagy-related proteins, such as ULK1, ATG13, AMBRA1, and ATG14L, which promote autophagy initiation and autophagosome nucleation. mTORC1 also phosphorylates and prevents nuclear localization of the transcription factor TFEB, a master regulator of lysosomal and autophagy gene expression. Proper lysosome function is essential for autophagy completion.