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Chuck Reynolds
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What does Resveratrol induce.? P-9, P-4

Published on 6/21/2019
For additional information  Click Here

Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition P-9


Liu et al. showed that resveratrol suppresses mTOR activity by enhancing the affinity between mTOR and DEPTOR, a negative regulator of mTOR. However, we observed no changes in the level of mTOR-interacting DEPTOR (supplementary Fig. S2). This discrepancy may be explained by the differences in experimental conditions. They used a pull-down assay of endogenous mTOR from C2C12, while we immunoprecipitated FLAG-mTOR from HEK293 cells. Additionally, active mTOR was reported to promote the degradation of DEPTOR. Thus, the increase in DEPTOR affinity may be due to the increased level of total DEPTOR proteins within cells due to resveratrol. Altogether, our study suggests that mTOR is a high-affinity direct target of resveratrol.

Resveratrol induces autophagy in various cell lines and in model organisms, such as Caenorhabditis elegans and mice5,6,7. In these reports, authors showed that autophagy induction is necessary for cancer cell death and alleviation of inflammation, and it may even extend the lifespan. Some studies showed decreased mTOR activity along with autophagy induction with resveratrol treatment, but there is no direct evidence suggesting that mTOR is a mediator of autophagy induction by resveratrol. In this study, using a combinatory chemical treatment and ULK1 knockdown, we clearly demonstrated that the mTOR-ULK1 pathway is necessary for autophagy induction by resveratrol.

In addition to resveratrol, other natural polyphenols, including quercetin and rottlerin also induce autophagy, possibly through mTOR. Further studies are necessary to examine the involvement of mTOR in autophagy induction by other natural polyphenols. Inhibition of mTOR has been shown to be a good strategy in the treatment of various illnesses, such as cancer, neurodegenerative diseases, and diabetes. This study will provide a basis for the identification of unknown mTOR-based effects of resveratrol.

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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