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Chuck Reynolds
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What does Resveratrol induce.? P-3

Published on 6/11/2019
For additional information  Click Here

Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition P-3

mTOR (the mammalian or mechanistic target of rapamycin),

a Ser/Thr kinase present in cells, functions within two distinct complexes: mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2). These complexes share mTOR as a kinase subunit, but contain different adaptors and scaffolds for distinct functions and regulatory mechanisms. mTORC1 controls cell growth and proliferation through the regulation of various processes and promotes translation through the phosphorylation of S6K and 4E-BP1. Lipid synthesis is also enhanced by active mTOR through the regulation of PPAR-γ, SREBP, and Lipin1. In addition to these anabolic processes, mTORC1 also suppresses catabolism by inhibiting autophagy.

Inhibition of mTORC1 is sufficient to induce autophagy, and nutrient-insensitive mTOR renders cells unresponsive to starvation-induced autophagy. Active mTOR inhibits autophagy by suppressing the ULK1-ATG13-FIP200 complex, specifically through the inhibitory phosphorylation of ULK1. Several studies have shown that resveratrol suppresses mTOR activity, which is expected to mediate resveratrol-induced autophagy. For the mechanism of inhibition, involvement of upstream regulators, including PI3K, AMPK, and SIRT1, has been suggested. However, conflicting results between these reports for the requirement of above-mentioned regulators in resveratrol-induced mTOR suppression result in ambiguity.

Here, we demonstrate that resveratrol induces autophagy through the mTOR-ULK1 pathway. Additionally, we found that resveratrol induces death of the cancer cells known to be sensitive to mTOR inhibition in ULK1 dependent manner. With respect to the mechanism by which resveratrol reduces mTOR activity, we demonstrated that resveratrol directly inhibits mTOR in an ATP-competitive manner. Through this study we suggest that mTOR is a distinct and direct target of resveratrol, and inhibition of mTOR is necessary for resveratrol-induced autophagy.

Article Produced By
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Republic of Korea

(All these Articles can be read with this URL: )

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Chuck Reynolds

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